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7/25/2019 Absorption and Bioavailability Purohit
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PHARMACOKINETICS:
I.ABSORPTION
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PHARMACOKINETICS
Dr.B.M.PUROHITAssistant Professor (Pharmao!o"#$
P.D.U.MEDICA% CO%%E&E'Ra)ot (&U*ARAT$. +,---
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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
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• This to7i is 6ni4ersa!!# ae7te3 asBORIN& 00
•So #o6 are free to fee! 5ore3 00
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000 &O S%O/ 00 Best!6) 000
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/HAT9S NE/ ABOUT IT 2222222..NOTHIN& 00
That9s the iron# 2222.thin"s are either re7eate3 or5orin" 000
MO;EMENT
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ABSORPTION
• =irst ste7.
• =or that 3r6" has to CROSSBIOLOGICAL MEMBRANES at
n6mero6s sites.
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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
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• P6!e3
• Nee3 a re4ision 2
• Remem5er 2222."o s!o> an3 as#o6 rea3' "o on remem5erin" it2
• Best !6) ..00
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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
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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.
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• 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
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Don’t
require
energy
Require
energy
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SUMMAR2
• Dr6" rosses mem5rane 5# 3i6sionan3 mem5rane trans7orters2..
• Di6sion an 5e !i7i3 or aF6o6s
• Mem5rane trans7orters an 5efai!itate3 or ati4ate3.
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PHSICA% PROPERTIES
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DOSA&E =ORMS
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• %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
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IONIJATION
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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 !!!!!
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7H
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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.
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&I transit time
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PRESENCE O= =OOD
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To 5e
ta)en5eforemea!s
To 5e
ta)enaftermea!s
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ENTEROHEPATICCIRCU%ATION
• Inreases the 5ioa4ai!a5i!it#.
• Mor7hine
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Area of the a5sor5in"s6rfae an3 !oa! ir6!ation
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=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"
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PRESENCE O= OTHERA&ENTS
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IO A"SO#TIO
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$AT SO%&"%E 'ITAMIES A"SO#TIO
E(&)E( I THE #ESE)E O$ %I*&I(
#AA$$I
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DISEASE CONDITIONS
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• /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
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SO ABSORPTION PART
IS O;ER2222222
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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$
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, o - , e - t r a t i o -
Tie
Mi-iu to/i,,o-,e-tratio-
Mi-iu e00e,ti1e
,o-,e-tratio-
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"ioa1ai2a3i2ity456 7
A&) a0ter ora2 dose
A&) a0ter I' dose
8 9::
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• 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".
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A!!7roesse
s ofPK 000
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• =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.
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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
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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#
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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.
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=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.
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DI==USION
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Hi;her
,o-,.
%o<er
,o-,.M
E
M
"
A
E
%i=id so2u32e
>ater
i-so2u32e
DI==USION
=I%TRATION
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%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.
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• 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.
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