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Pharmacokinetics workshop
MohammedEl-SakkarMSc (Pediatrics), MD, PhD (Pharmacology)
Allergy & Immunology consultantProfessor of Pharmacology
University of Alexandria
2013
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If a patient taking 0.25 mg tablet of digoxin daily, requires IV
administration of the drug.
What would an equivalent dose be? When F for tablet is 0.62.
F for I.V. doses is 1
F for tablet is 0.62
Amount reach to circulation intact = 0.25 X 0.62 = 0.155 mg
I.V. dose = 0.155 mg
Amount reach to systemic circulation intact = Dose (extravascular) X F
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What is the equivalent dosage of oral theophylline for a patient
receiving IV aminophylline at a rate of 80 mg/hr?
N.B theophylline is completely absorbed on oral administrationand 80% of aminophylline weight is theophylline.
I.V. aminophylline dose per day= 80 x 24 = 1920 mg/day
TheophyllineAminophylline
80100
?1920
Oral theophylline dose = 1920x 80 = 1536 mg/day
100
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A normal volunteer will receive a new drug in a phase I clinical
trial. The clearance and volume of distribution of the drug in
this subject are 1.386 L/h and 80 L, respectively. The half life
of the drug in this subject will be approximately
t =Cl
0.693 X Vd
t
= 1.386 L/h
0.693 X 80 L
= 40 h
Cl = 1.386 L/h Vd = 80 L
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Estimate the oral loading dose of digoxin for a 70 kg man, which
would be necessary to attain a plasma level of 1.5 g/L
(microgram/L)? Vd of digoxin is reduced to 420 L, F for tablet is0.62
Loading dose=X Desired initial plasma concentration (amount/vol)Vd
Bioavailability (F)
420 (L) X 1.5 g/L
0.62= 1016 g
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What is the apparent clearance of lidocaine in a patient who is
receiving an IV infusion of 2 mg/min and has a steady state
plasma level of 3 mg/L? (Given is: Vd = 7.3 L/Kg and F = 0.7)
Maintenance dosing rate =
(amount/time)
X Cl (vol/time)Desired Plasma drug concentration ss
(Cpss)
Bioavailability (F)
= 40 L/h
Clearance (Cl) =Maintenance dosing rate x F
Cpss
120 mg/h
3 mg/L=
Clearance (Cl) =120 mg/h x 1
3 mg/L
120 mg/h
3 mg/L=
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Alia is a 70 year-old 68 kg with CHF and chronic renal failure
(Clcr25ml/min). It is decided that a loading dose of digoxin is to
be administered orally. What must you consider in calculating
the estimated loading dose? The desired Cp is 1.5 microgram/L,Vd of digoxin is reduced to 4.7L/kg, F for tablet is 0.62
Loading dose=X Desired initial plasma concentration (amount/vol)Vd
Bioavailability (F)
4.7 L x 68 kg X 1.5 g/L
0.62 = 773g
Corrected dose = Average dosePatients creatinine clearance
100 mL/minX
Corrected dose in RF = 773 gX
25
100 = 193.25 g
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What will be an appropriate maintenance infusion rate of
aminophylline to keep the plasma level at 15 mcg/ml? The
clearance of theophylline in arithmetic adults is 4.73L/hr
Maintenance dosing rate =
(amount/time)
X Cl(vol/time)Cpss
Bioavailability (F)
15 mg/L X 4.73L/hr
1 = 70.95 mg/h theophylline
Aminophylline maintemance dose = 70.95 x 100/80 = 88.6 mg/h
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Loading dose =Vd x Target concentration
Bioavailability (F)
A 70 kg patient states she ingested approximately 30 tablets of
phenobarbitone each contain 100mg. Vd listed is 0.75 L/kg. Peak
blood concentration measured by the lab is 60 mg/L, F=1. How
can you verify the history?
0.75 x 70x 60
1= 3150 mg=
= 3000 mg
The history is correct
She say 30x 100 =
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Loading dose =Vd x Target concentration
Bioavailability (F)
A 70 kg patient states she ingested approximately 30 tablets of
phenobarbitone each contain 100mg. Vd listed is 0.75 L/kg. Peak
blood concentration measured by the lab is 60 mg/L, F=1. How
can you verify the history?
Target concentration =LD x F
Vd
3000 x 1
0.75 x 70= 57 mg/L=
The history is correct
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A 70 kg patient ingested an unknown number of lithium cap (300
mg = 8 mEq) and has a peak concentration of 5 mEq/L . The
patient is now agitated. What is the number of capsules
ingested? Its Vd is 0.7L/kg, F=1.
Loading dose =Vd x Target concentration
Bioavailability (F)
(0.7 x 70) x 5 mEq/L = 245 mEq
Number of capsules ingested = 245 mEq8 mEq
= 30 cap of 300 mg
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Despite your careful adherence to basic pharmacokinetic
principles, your patient on digoxin therapy has developed
digitalis toxicity. The plasma digoxin level is 4 ng/mL. Renal
function is normal, and the plasma t for digoxin in thispatient is 1.6 days. How long should you withhold digoxin in
order to reach a safer yet probably therapeutic level of 1
ng/mL?
Since the blood level for a drug with first-order kinetics drops by 50%
during each half-life, the level will be 2 ng/mL after 1.6 days and 1 ng/mL
after 3.2 days.
0 2 64 8 2 64 8 100
25
75
50
100
%
ofmaximum
Time (number of half-lives)
Start
infusion
Stop
infusion
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A new drug was studied in 20 healthy volunteers to determine basic
pharmacokinetic parameters. A dose of 100 mg was administered as an
intravenous bolus to each volunteer and blood samples were analyzed at
intervals as shown in the graph below. The average plasma concentrations
at each time are shown by the solid circles at 10 and 30 minutes and at 1,
2, 3, 4, 6, and 8 hours after administration.
Determine :
Elimination half life
Vd
Clearance
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The elimination phase of the graph of plasma concentration follows a
straight line on the semi logarithmic graph, so we can conclude that the
new drug follows first-order kinetics, the first requirement for determining
the half-life.The straight-line portion of the graph shows a decline of 50% from the 2-
hour point (4 mglL) to the 8-hour sample (2 mglL).
Half-life = 8 hs minus 2 hours = 6 hours.
Loading doseVd =
X Bioavailability (F)
Target concentration (Cp0)
100 mg x 1
5 mg/L= 20 L
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t =Cl
0.693 X Vd
tCl = 0.693 X Vd
6 hCl =
0.693 X 20L= 2.3 L/h
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