absorption and bioavailability purohit

7/25/2019 Absorption and Bioavailability Purohit

http://slidepdf.com/reader/full/absorption-and-bioavailability-purohit 1/48

PHARMACOKINETICS:

I.ABSORPTION



PHARMACOKINETICS

Dr.B.M.PUROHITAssistant Professor (Pharmao!o"#$

P.D.U.MEDICA% CO%%E&E'Ra)ot (&U*ARAT$. +,---

[email protected]

&O S%O/ 00 &O ONREMEMBERIN& 000

1

• This is not a %ECTURE22222this isa discussion2 sa3!# 2 not !i4e 000

•O5eti4e is not to 5om5ar3information 56t to develop

concepts2.

•So.. &et rea3# to hat 00



• This to7i is 6ni4ersa!!# ae7te3 asBORIN& 00

•So #o6 are free to fee! 5ore3 00


+



000 &O S%O/ 00 Best!6) 000


8



/HAT9S NE/ ABOUT IT 2222222..NOTHIN& 00

That9s the iron# 2222.thin"s are either re7eate3 or5orin" 000

MO;EMENT


<



ABSORPTION

• =irst ste7.

• =or that 3r6" has to CROSSBIOLOGICAL MEMBRANES at

n6mero6s sites.


,



A5sor7tion

CENTRA% COMPARTMENT

Un>ante3 site ofation

=ree ? 5o6n3

BiotransformationSite of ation=ree ? 5o6n3

TISSUE RESER;OIR=ree ? 5o6n3

=REE DRU&

E@retion

METABO%ITES

Protein5o6n3




• P6!e3

• Nee3 a re4ision 2

• Remem5er 2222."o s!o> an3 as#o6 rea3' "o on remem5erin" it2

• Best !6) ..00




A5sor7tion

CENTRA% COMPARTMENT

Un>ante3 site ofation

=ree ? 5o6n3

BiotransformationSite of ation=ree ? 5o6n3

TISSUE RESER;OIR=ree ? 5o6n3

=REE DRU&

E@retion

METABO%ITES

Protein5o6n3




SUMMAR O= DIA&RAM

• So2 after a5sor7tion2.

– A 7art ma# "et excretedexcreted 6nhan"e3.

– A 7art ma# 5e metabolized and than excretedmetabolized and than excreted.

– A 7art >i!! reversibly 5in3 >ith the site ofsite ofactionaction.

– A 7art >i!! reversibly "o to tissue reservoirstissue reservoirs.

– A 7art >i!! reversibly "o to unwanted site ofunwanted site of

actionaction..

– A 7art >i!! reversibly 5in3 >ith plasma plasma

proteins proteins.


-



• A!! this thin"s ha77en after ABSORPTION2

• Mi!!ion 3o!!ar F6estion222..Mi!!ion 3o!!ar F6estion222..

–Ho> EGTERNA%% a3ministere3 3r6"

CROSSES BIOLOIC!L"E"BR!#ES ( THEIR MO%ECU%AR MECHANISMS$22.

• No> ima$ine a molecule tr%in$ to cross aima$ine a molecule tr%in$ to cross a

biolo$ical membranebiolo$ical membrane.

• So a mo!e6!e an3 a mem5rane are "htin" >itheah other 0000




Don’t

require

energy

Require

energy


1



SUMMAR2

• Dr6" rosses mem5rane 5# 3i6sionan3 mem5rane trans7orters2..

• Di6sion an 5e !i7i3 or aF6o6s

• Mem5rane trans7orters an 5efai!itate3 or ati4ate3.


+




8




<




,



PHSICA% PROPERTIES




DOSA&E =ORMS


Better7aramet

er



• %ets re4ise 3r6" re!ate3 fators2

• Ph#sia! 7ro7erties

–Ph#sia! state – %i7i3 or >ater so!65i!it#

• Dosa"e forms

– Parti!e sie – Disinte"ration an3 3isso!6tion rate

– =orm6!ation





1-



IONIJATION


1

TAKE HOME MESSAGE ……..

““UNIONIZED FORM IS BETTERUNIONIZED FORM IS BETTER

ABSORBED ABSORBED”……………..store it you’re”……………..store it you’re

your hard disk !!!!!your hard disk !!!!!



7H


11

A!tho6"h ai3i 3r6" are 5etter

a5sor5e3 from stomah ' a !ar"e7ortion of it "ets a5sor5e3 thro6"hthe intestine 5ea6se of "reaters6rfae area it 7ro4i3es.



&I transit time


1+



PRESENCE O= =OOD


18

To 5e

ta)en5eforemea!s

To 5e

ta)enaftermea!s



ENTEROHEPATICCIRCU%ATION

• Inreases the 5ioa4ai!a5i!it#.

• Mor7hine


1<



Area of the a5sor5in"s6rfae an3 !oa! ir6!ation


1,



=IRST PASS METABO%ISM

• Meta5o!ism 5et>een site of a5sor7tionto that of s#stemi ir6!ation.

• Dereases the 5ioa4ai!a5i!it# of 3r6"s.

• It ta)es 7!ae in

– &6t >a!!

– %i4er

– S)in

– %6n"


1



PRESENCE O= OTHERA&ENTS


1

IO A"SO#TIO




1

$AT SO%&"%E 'ITAMIES A"SO#TIO

E(&)E( I THE #ESE)E O$ %I*&I(

#AA$$I



DISEASE CONDITIONS


+-



• /hih are drug releated actors aetin" 3r6"a5sor7tion

– Ph#sia! 7ro7erties

– Dosa"e forms.• /hih patient related actors2

– Ioniation

– 7H

– &I transit time

– Presene of foo3

– Enterohe7ati ir6!ation

– Area of a5sor5in" s6rfae

– =irst 7ass meta5o!ism

– Presene of other a"ents.

– Disease3 on3itions


+

+




+1

SO ABSORPTION PART

IS O;ER2222222



BIOA;AI%ABI%IT

• percent of administered dru$ reachin$ s%stemiccirculation followin$ nonvascular administration.L

• E.". if <-- m" 3r6" is "i4en an3 <- m" reahess#stemi ir6!ation 5ioa4ai!a5i!it# is -.

• It is im7ortant in 2.

– Dr6" >ith low saety marginlow saety margin.( e.". 3i"o@in$ – Dr6" >here specic plasma levels arespecic plasma levels are

necessarynecessary. (ora! h#7o"!#emi' ora!antioa"6!ants' ora! antie7i!e7tis$


++




+8

, o - , e - t r a t i o -

Tie

Mi-iu to/i,,o-,e-tratio-

Mi-iu e00e,ti1e

,o-,e-tratio-




+<

"ioa1ai2a3i2ity456 7

A&) a0ter ora2 dose

A&) a0ter I' dose

8 9::



• I administration Bioa4ai!a5i!it#>i!! 5e -- .

• !ral administration BA3ereases 5ea6se of..

– Inom7!ete a5sor7tion

– =irst 7ass meta5o!ism.

• "# or I$ administrationInom7!ete BA after inetion

o6rs 5ea6se of !oa! 5in3in" of3r6".


+,




+




+

A!!7roesse

s ofPK 000



• =or e4er# t>o mar)et form6!ations of the same ati4e 3r6"'5ioa4ai!a5i!it# >i!! 5e DE=INITE% DI==ERENT.DE=INITE% DI==ERENT.

• This 3ierene ma# not 5e C%INICA% SI&NI=ICANTma# not 5e C%INICA% SI&NI=ICANT.


+




8-

Dr6"s !i)eantioa"6!an

ts'antie7i!e7tis

"o %" &%R %""o %" &%R %"

'!""I()* %!ID'!""I()* %!ID

#+%,-I,-#+%,-I,-

(R%,D" in(R%,D" in

"/#+ #%"*".0"/#+ #%"*".0



NO/ IT9S TIME TO RE;ISE

• /hat is 5ioa4ai!a5i!it#

• /hen this 7arameter 5eomessi"niant

• /hat is 3ierene 5et>een BA of I;'ora!' SC or IM ro6te

• /hat is hemia! eF6i4a!ent

• /hat is 5io!o"ia! eF6i4a!ent

• /hih fators aet 5ioa4ai!a5i!it#


8



MEMBRANE TRANSPORT

• Bi!a#er of 7hos7ho!i7i3 an3ho!estero!.

• Po!ar "ro67s on s6rfaes

• Non 7o!ar "ro67s in matri@.

• E@trinsi an3 intrinsi 7rotein area3sor5e3 on !i7i3 5i!a#er.

• Proteins free!# oat thro6"h themem5rane.

&O S%O/ 00 &O ONREMEMBERIN& 000 81



&O S%O/ 00 &O ONREMEMBERIN& 000 8+



=I%TRATION

• Thro6"h 7ores.

• &enera!!# 7ores are sma!! e@e7ta7i!!aries.

• M/-- an 7ass thro6"h it.

• Ca7i!!aries ha4e !ar"e 7ores' e@e7tBBB.




DI==USION

&O S%O/ 00 &O ONREMEMBERIN& 000 8<

Hi;her

,o-,.

%o<er

,o-,.M

E

M

"

A

E

%i=id so2u32e

>ater

i-so2u32e

DI==USION

=I%TRATION



%1/*!/" DI&&/"I!,

• Most 5io!o"ia!

mem5ranes are >ater7ermea5!e.

• In "6t' e!!s are oine3ti"ht e7ithe!ia!

6ntion' >ater 7assesthro6"h the e!!s.

• /ater arries >aterso!65!e s65stanes of%M/.

• Urea' a!oho!

)I'ID DI&&/"I!,

• H#3ro7ho5i !i7i3

s65stanes are3isso!4e3 in thismanner.

• O1'CO1'N1' 6nionie3

s65stanes.

&O S%O/ 00 &O ONREMEMBERIN& 000 8,



• Passi4e 3i6sion o6rs thro6"hPassi4e 3i6sion o6rs thro6"h..

– Conentration "ra3ient

– %i7i3 so!65i!it#.

• %i7i3 so!65i!it# ioniation

• Ionie3 >ater so!65!e nota5sor5e3.

• Unionie3 !i7i3 so!65!e 5ettera5sor5e3.


absorption and bioavailability purohit

Documents