pharmacokinetic parameters.ppt
DESCRIPTION
pharmacokinetic parameters pharmacology half life VdTRANSCRIPT
LOGO
Pharmacokinetic Parameters
Muhammad Faisal Nadeem
wwwthemegallerycom
Company Logo
Bioavailability
Dose
Destroyed in gut
Notabsorbed
Destroyed by gut wall
Destroyedby liver
tosystemiccirculation
wwwthemegallerycom
Company Logo
The ldquotrue doserdquo is not the drug swallowedBUT is the drug available to exert its effectbull1048708 Dissolutionbull1048708 Absorptionbull1048708 Survive metabolismMay have a drug with very low bioavailabilitybull1048708 Dosage form or drug may not dissolve readilybull1048708 Drug may not be readily pass across biological membranes (ie be absorbed)bull1048708 Drug may be extensively metabolized during absorption process (first-pass gut wall liver)Important component of overall variabilitybull1048708 Variable bioavailability may produce variable exposure
Why do we care about BIOAVAILABILITY
wwwthemegallerycom
Company Logo
Dose
Pla
sm
a C
on
cen
tratio
n
0 1 2 3 4 5 6 7 8 90
2
4
6
8
10
12
TOXIC RANGE
THERAPEUTIC RANGE
SUB-THERAPEUTIC
wwwthemegallerycom
Company Logo
Bound Free Free Bound
LOCUS OF ACTION
ldquoRECEPTORSrdquoTISSUE
RESERVOIRS
SYSTEMIC CIRCULATION
Free Drug
Bound Drug
ABSORPTION EXCRETION
BIOTRANSFORMATION
wwwthemegallerycom
Company Logo
Plasma concentration vs time profile of a single dose of a drug ingested orally
0
2
4
6
8
10
12
14
0 5 10 15 20
TIME (hours)
Pla
sm
a C
on
cen
tra
tio
n
wwwthemegallerycom
Company Logo
FACTORS INFLUENCING BIOAVAILABILITY
Three distinct factors are involved to influencing bioavailability These are
1Pharmaceutical factors physicochemical properties of the drug 1 Particle size 2 Crystalline structure3 Salt form Formulation and manufacturing variables1Disintegration and dissolution time2Pharmaceutical ingredients 3Special coatings4Nature and type of dosage form
wwwthemegallerycom
Company Logo
2 Patient related factors
Physiologic factors 1Variations in pH of GI fluids 2Gastric emptying rate 3 Intestinal motility 4 Presystemic and first-pass metabolism 5 Age sex 6 Disease states Interactions with other substances 1 Food 2 Fluid volume 3 Other drugs3 Route of administration 1Parentral administration 2Oral administration 3Rectal administration 4Topical administration
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
frac12 life = how much time it takes for blood levels of drug to decrease to half of what it was at equilibrium
There are really two kinds of frac12 lifehellipldquodistributionrdquo frac12 life = when plasma levels fall
to half what they were at equilibrium due to distribution tostorage in bodyrsquos tissue reservoirs
ldquoeliminationrdquo frac12 life = when plasma levels fall to half what they were at equilibrium due to drug being metabolized and eliminated
It is usually the elimination frac12 life that is used to determine dosing schedules to decide when it is safe to put patients on a new drug
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Bioavailability
Dose
Destroyed in gut
Notabsorbed
Destroyed by gut wall
Destroyedby liver
tosystemiccirculation
wwwthemegallerycom
Company Logo
The ldquotrue doserdquo is not the drug swallowedBUT is the drug available to exert its effectbull1048708 Dissolutionbull1048708 Absorptionbull1048708 Survive metabolismMay have a drug with very low bioavailabilitybull1048708 Dosage form or drug may not dissolve readilybull1048708 Drug may not be readily pass across biological membranes (ie be absorbed)bull1048708 Drug may be extensively metabolized during absorption process (first-pass gut wall liver)Important component of overall variabilitybull1048708 Variable bioavailability may produce variable exposure
Why do we care about BIOAVAILABILITY
wwwthemegallerycom
Company Logo
Dose
Pla
sm
a C
on
cen
tratio
n
0 1 2 3 4 5 6 7 8 90
2
4
6
8
10
12
TOXIC RANGE
THERAPEUTIC RANGE
SUB-THERAPEUTIC
wwwthemegallerycom
Company Logo
Bound Free Free Bound
LOCUS OF ACTION
ldquoRECEPTORSrdquoTISSUE
RESERVOIRS
SYSTEMIC CIRCULATION
Free Drug
Bound Drug
ABSORPTION EXCRETION
BIOTRANSFORMATION
wwwthemegallerycom
Company Logo
Plasma concentration vs time profile of a single dose of a drug ingested orally
0
2
4
6
8
10
12
14
0 5 10 15 20
TIME (hours)
Pla
sm
a C
on
cen
tra
tio
n
wwwthemegallerycom
Company Logo
FACTORS INFLUENCING BIOAVAILABILITY
Three distinct factors are involved to influencing bioavailability These are
1Pharmaceutical factors physicochemical properties of the drug 1 Particle size 2 Crystalline structure3 Salt form Formulation and manufacturing variables1Disintegration and dissolution time2Pharmaceutical ingredients 3Special coatings4Nature and type of dosage form
wwwthemegallerycom
Company Logo
2 Patient related factors
Physiologic factors 1Variations in pH of GI fluids 2Gastric emptying rate 3 Intestinal motility 4 Presystemic and first-pass metabolism 5 Age sex 6 Disease states Interactions with other substances 1 Food 2 Fluid volume 3 Other drugs3 Route of administration 1Parentral administration 2Oral administration 3Rectal administration 4Topical administration
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
frac12 life = how much time it takes for blood levels of drug to decrease to half of what it was at equilibrium
There are really two kinds of frac12 lifehellipldquodistributionrdquo frac12 life = when plasma levels fall
to half what they were at equilibrium due to distribution tostorage in bodyrsquos tissue reservoirs
ldquoeliminationrdquo frac12 life = when plasma levels fall to half what they were at equilibrium due to drug being metabolized and eliminated
It is usually the elimination frac12 life that is used to determine dosing schedules to decide when it is safe to put patients on a new drug
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
The ldquotrue doserdquo is not the drug swallowedBUT is the drug available to exert its effectbull1048708 Dissolutionbull1048708 Absorptionbull1048708 Survive metabolismMay have a drug with very low bioavailabilitybull1048708 Dosage form or drug may not dissolve readilybull1048708 Drug may not be readily pass across biological membranes (ie be absorbed)bull1048708 Drug may be extensively metabolized during absorption process (first-pass gut wall liver)Important component of overall variabilitybull1048708 Variable bioavailability may produce variable exposure
Why do we care about BIOAVAILABILITY
wwwthemegallerycom
Company Logo
Dose
Pla
sm
a C
on
cen
tratio
n
0 1 2 3 4 5 6 7 8 90
2
4
6
8
10
12
TOXIC RANGE
THERAPEUTIC RANGE
SUB-THERAPEUTIC
wwwthemegallerycom
Company Logo
Bound Free Free Bound
LOCUS OF ACTION
ldquoRECEPTORSrdquoTISSUE
RESERVOIRS
SYSTEMIC CIRCULATION
Free Drug
Bound Drug
ABSORPTION EXCRETION
BIOTRANSFORMATION
wwwthemegallerycom
Company Logo
Plasma concentration vs time profile of a single dose of a drug ingested orally
0
2
4
6
8
10
12
14
0 5 10 15 20
TIME (hours)
Pla
sm
a C
on
cen
tra
tio
n
wwwthemegallerycom
Company Logo
FACTORS INFLUENCING BIOAVAILABILITY
Three distinct factors are involved to influencing bioavailability These are
1Pharmaceutical factors physicochemical properties of the drug 1 Particle size 2 Crystalline structure3 Salt form Formulation and manufacturing variables1Disintegration and dissolution time2Pharmaceutical ingredients 3Special coatings4Nature and type of dosage form
wwwthemegallerycom
Company Logo
2 Patient related factors
Physiologic factors 1Variations in pH of GI fluids 2Gastric emptying rate 3 Intestinal motility 4 Presystemic and first-pass metabolism 5 Age sex 6 Disease states Interactions with other substances 1 Food 2 Fluid volume 3 Other drugs3 Route of administration 1Parentral administration 2Oral administration 3Rectal administration 4Topical administration
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
frac12 life = how much time it takes for blood levels of drug to decrease to half of what it was at equilibrium
There are really two kinds of frac12 lifehellipldquodistributionrdquo frac12 life = when plasma levels fall
to half what they were at equilibrium due to distribution tostorage in bodyrsquos tissue reservoirs
ldquoeliminationrdquo frac12 life = when plasma levels fall to half what they were at equilibrium due to drug being metabolized and eliminated
It is usually the elimination frac12 life that is used to determine dosing schedules to decide when it is safe to put patients on a new drug
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Dose
Pla
sm
a C
on
cen
tratio
n
0 1 2 3 4 5 6 7 8 90
2
4
6
8
10
12
TOXIC RANGE
THERAPEUTIC RANGE
SUB-THERAPEUTIC
wwwthemegallerycom
Company Logo
Bound Free Free Bound
LOCUS OF ACTION
ldquoRECEPTORSrdquoTISSUE
RESERVOIRS
SYSTEMIC CIRCULATION
Free Drug
Bound Drug
ABSORPTION EXCRETION
BIOTRANSFORMATION
wwwthemegallerycom
Company Logo
Plasma concentration vs time profile of a single dose of a drug ingested orally
0
2
4
6
8
10
12
14
0 5 10 15 20
TIME (hours)
Pla
sm
a C
on
cen
tra
tio
n
wwwthemegallerycom
Company Logo
FACTORS INFLUENCING BIOAVAILABILITY
Three distinct factors are involved to influencing bioavailability These are
1Pharmaceutical factors physicochemical properties of the drug 1 Particle size 2 Crystalline structure3 Salt form Formulation and manufacturing variables1Disintegration and dissolution time2Pharmaceutical ingredients 3Special coatings4Nature and type of dosage form
wwwthemegallerycom
Company Logo
2 Patient related factors
Physiologic factors 1Variations in pH of GI fluids 2Gastric emptying rate 3 Intestinal motility 4 Presystemic and first-pass metabolism 5 Age sex 6 Disease states Interactions with other substances 1 Food 2 Fluid volume 3 Other drugs3 Route of administration 1Parentral administration 2Oral administration 3Rectal administration 4Topical administration
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
frac12 life = how much time it takes for blood levels of drug to decrease to half of what it was at equilibrium
There are really two kinds of frac12 lifehellipldquodistributionrdquo frac12 life = when plasma levels fall
to half what they were at equilibrium due to distribution tostorage in bodyrsquos tissue reservoirs
ldquoeliminationrdquo frac12 life = when plasma levels fall to half what they were at equilibrium due to drug being metabolized and eliminated
It is usually the elimination frac12 life that is used to determine dosing schedules to decide when it is safe to put patients on a new drug
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Bound Free Free Bound
LOCUS OF ACTION
ldquoRECEPTORSrdquoTISSUE
RESERVOIRS
SYSTEMIC CIRCULATION
Free Drug
Bound Drug
ABSORPTION EXCRETION
BIOTRANSFORMATION
wwwthemegallerycom
Company Logo
Plasma concentration vs time profile of a single dose of a drug ingested orally
0
2
4
6
8
10
12
14
0 5 10 15 20
TIME (hours)
Pla
sm
a C
on
cen
tra
tio
n
wwwthemegallerycom
Company Logo
FACTORS INFLUENCING BIOAVAILABILITY
Three distinct factors are involved to influencing bioavailability These are
1Pharmaceutical factors physicochemical properties of the drug 1 Particle size 2 Crystalline structure3 Salt form Formulation and manufacturing variables1Disintegration and dissolution time2Pharmaceutical ingredients 3Special coatings4Nature and type of dosage form
wwwthemegallerycom
Company Logo
2 Patient related factors
Physiologic factors 1Variations in pH of GI fluids 2Gastric emptying rate 3 Intestinal motility 4 Presystemic and first-pass metabolism 5 Age sex 6 Disease states Interactions with other substances 1 Food 2 Fluid volume 3 Other drugs3 Route of administration 1Parentral administration 2Oral administration 3Rectal administration 4Topical administration
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
frac12 life = how much time it takes for blood levels of drug to decrease to half of what it was at equilibrium
There are really two kinds of frac12 lifehellipldquodistributionrdquo frac12 life = when plasma levels fall
to half what they were at equilibrium due to distribution tostorage in bodyrsquos tissue reservoirs
ldquoeliminationrdquo frac12 life = when plasma levels fall to half what they were at equilibrium due to drug being metabolized and eliminated
It is usually the elimination frac12 life that is used to determine dosing schedules to decide when it is safe to put patients on a new drug
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Plasma concentration vs time profile of a single dose of a drug ingested orally
0
2
4
6
8
10
12
14
0 5 10 15 20
TIME (hours)
Pla
sm
a C
on
cen
tra
tio
n
wwwthemegallerycom
Company Logo
FACTORS INFLUENCING BIOAVAILABILITY
Three distinct factors are involved to influencing bioavailability These are
1Pharmaceutical factors physicochemical properties of the drug 1 Particle size 2 Crystalline structure3 Salt form Formulation and manufacturing variables1Disintegration and dissolution time2Pharmaceutical ingredients 3Special coatings4Nature and type of dosage form
wwwthemegallerycom
Company Logo
2 Patient related factors
Physiologic factors 1Variations in pH of GI fluids 2Gastric emptying rate 3 Intestinal motility 4 Presystemic and first-pass metabolism 5 Age sex 6 Disease states Interactions with other substances 1 Food 2 Fluid volume 3 Other drugs3 Route of administration 1Parentral administration 2Oral administration 3Rectal administration 4Topical administration
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
frac12 life = how much time it takes for blood levels of drug to decrease to half of what it was at equilibrium
There are really two kinds of frac12 lifehellipldquodistributionrdquo frac12 life = when plasma levels fall
to half what they were at equilibrium due to distribution tostorage in bodyrsquos tissue reservoirs
ldquoeliminationrdquo frac12 life = when plasma levels fall to half what they were at equilibrium due to drug being metabolized and eliminated
It is usually the elimination frac12 life that is used to determine dosing schedules to decide when it is safe to put patients on a new drug
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
FACTORS INFLUENCING BIOAVAILABILITY
Three distinct factors are involved to influencing bioavailability These are
1Pharmaceutical factors physicochemical properties of the drug 1 Particle size 2 Crystalline structure3 Salt form Formulation and manufacturing variables1Disintegration and dissolution time2Pharmaceutical ingredients 3Special coatings4Nature and type of dosage form
wwwthemegallerycom
Company Logo
2 Patient related factors
Physiologic factors 1Variations in pH of GI fluids 2Gastric emptying rate 3 Intestinal motility 4 Presystemic and first-pass metabolism 5 Age sex 6 Disease states Interactions with other substances 1 Food 2 Fluid volume 3 Other drugs3 Route of administration 1Parentral administration 2Oral administration 3Rectal administration 4Topical administration
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
frac12 life = how much time it takes for blood levels of drug to decrease to half of what it was at equilibrium
There are really two kinds of frac12 lifehellipldquodistributionrdquo frac12 life = when plasma levels fall
to half what they were at equilibrium due to distribution tostorage in bodyrsquos tissue reservoirs
ldquoeliminationrdquo frac12 life = when plasma levels fall to half what they were at equilibrium due to drug being metabolized and eliminated
It is usually the elimination frac12 life that is used to determine dosing schedules to decide when it is safe to put patients on a new drug
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
2 Patient related factors
Physiologic factors 1Variations in pH of GI fluids 2Gastric emptying rate 3 Intestinal motility 4 Presystemic and first-pass metabolism 5 Age sex 6 Disease states Interactions with other substances 1 Food 2 Fluid volume 3 Other drugs3 Route of administration 1Parentral administration 2Oral administration 3Rectal administration 4Topical administration
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
frac12 life = how much time it takes for blood levels of drug to decrease to half of what it was at equilibrium
There are really two kinds of frac12 lifehellipldquodistributionrdquo frac12 life = when plasma levels fall
to half what they were at equilibrium due to distribution tostorage in bodyrsquos tissue reservoirs
ldquoeliminationrdquo frac12 life = when plasma levels fall to half what they were at equilibrium due to drug being metabolized and eliminated
It is usually the elimination frac12 life that is used to determine dosing schedules to decide when it is safe to put patients on a new drug
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
frac12 life = how much time it takes for blood levels of drug to decrease to half of what it was at equilibrium
There are really two kinds of frac12 lifehellipldquodistributionrdquo frac12 life = when plasma levels fall
to half what they were at equilibrium due to distribution tostorage in bodyrsquos tissue reservoirs
ldquoeliminationrdquo frac12 life = when plasma levels fall to half what they were at equilibrium due to drug being metabolized and eliminated
It is usually the elimination frac12 life that is used to determine dosing schedules to decide when it is safe to put patients on a new drug
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Concept of ldquoHalf Liferdquo
Time [hours]
0 4 8 12 16 20 24
Co
nc
[mg
L]
0
1
2
3
4
5
wwwthemegallerycom
Company Logo
Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
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wwwthemegallerycom
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FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
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FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
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Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
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Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
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Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
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Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
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LOGO
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Elimination
Zero order constant rate of elimination irrespective of plasma concentration
First order rate of elimination proportional to plasma concentration Constant Fraction of drug eliminated per unit time
Rate of elimination prop AmountRate of elimination = K x Amount
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Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
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C
t
Cpav
Four half lives to reach steady state
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Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
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Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
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Constant Rate of Administration (iv)
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Loading Dose
Dose = Cp(Target) x VD
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Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
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Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Multiple dosing
On continuous steady administration of a drug plasma concentration will rise fast at first then more slowly and reach a plateau where
rate of administration = rate of elimination ie steady state is reached
Therefore at steady stateDose (Rate of Administration) = clearance x plasma conc
OrIf you aim at a target plasma level and you know the
clearance you can calculate the dose required
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
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Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
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Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
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Constant Rate of Administration (iv)
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Loading Dose
Dose = Cp(Target) x VD
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Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
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Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
C
t
Cpav
Four half lives to reach steady state
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
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Company Logo
Constant Rate of Administration (iv)
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Company Logo
Loading Dose
Dose = Cp(Target) x VD
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Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
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Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30
Time
Pla
sma
Co
nce
ntr
atio
n
Repeated doses ndashMaintenance dose
Therapeutic level
Single dose ndash Loading dose
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
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Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Multiple Dose Administration
Minimum and maximum conc should be within therapeutic window ndash depends on dose frequency and t12
Depending on dosing frequency and t12 accumulation occurs Degree of accumulation is important for safety assessment
purposes
Time (hr)
Con
cen
trati
on
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Constant Rate of Administration (iv)
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Loading Dose
Dose = Cp(Target) x VD
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Maintenance Dose Calculation
Maintenance Dose = CL x CpSSav
CpSSav is the target average steady state drug concentration
The units of CL are in Lhr or Lhrkg
Maintenance dose will be in mghr so for total daily dose will need multiplying by 24
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Bioequivalence
A comparison of the bioavailability of two or more drug products
Two products or formulations containing the same active ingredient are bioequivalent if their rates and extents of absorption are the same
Bioequivalence may be demonstrated through in vivo or in vitro test methods comparative clinical trials or pharmacodynamic studies
wwwthemegallerycom
Company Logo
Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
wwwthemegallerycom
Company Logo
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
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Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
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Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
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Bioequivalence
Definition - CFR 3201It is the absence of significance difference in the rate and extent to which active ingredient or active moiety in pharmaceutical equivalent or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study
Note BE has a specific definition and regulatory requirements BE is not the same as the BA
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FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
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FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
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Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
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Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
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Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
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Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
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Company Logo
LOGO
wwwthemegallerycom
Company Logo
wwwthemegallerycom
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FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
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Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
FDA Methods to Determine Bioequivalence
Generic drug manufacturers must demonstrate that a drug is bioequivalent to a reference drug product
In order of FDA preference methods used to define bioequivalence Pharmacokinetic studies Pharmacodynamic studies Comparative clinical trials In vitro studies
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
FDA Determinations of Bioequivalence
Main Terms
Pharmaceutical equivalentsPharmaceutical alternativesTherapeutic equivalentsBioavailabilityBioequivalence
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Pharmaceutical Equivalents
Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s) have the same dosage form and route of administration and are identical in strength or concentration
Equivalent products contain the same amount of ingredient in the same dosage form but may differ in characteristics such as shape release mechanisms and packaging
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Pharmaceutical Alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety are different salts esters or complexes of the same moiety are different dosage forms or are different strengths
Other pharmaceutical alternatives Different dosage forms and strengths within a single product line
by a single manufacturer Extended-release formulations when compared with immediate-
or standard-release formulations
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Therapeutic Equivalents
Drug products are considered therapeutic equivalents if they are all of the following Pharmaceutical equivalents Bioequivalent Approved as safe and effective Adequately labeled Manufactured in compliance with current Good Manufacturing
Practice regulations
Therapeutic equivalents are expected to have the same clinical effect and safety profile
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
Therapeutic Index
Therapeutic index = toxic doseeffective dose
This is a measure of a drugrsquos safety A large number = a wide margin of safety A small number = a small margin of safety
wwwthemegallerycom
Company Logo
LOGO
wwwthemegallerycom
Company Logo
LOGO
LOGO