Zero order and first order kinetiks

These slides explain the basics of zero order and first order pharmacokinetics using text, few original images (i took from net, not my creation)

1. Zero order & first order
pharmacokinetics
Available on Slideshare
from May 09, 2017 09.30 PM
Amit ka PPT
(Amit’s PPT)
Dr. Amit Ratn Gangwal Jain
(MPharm., PhD.)

2. Absorption of drug

3. ThesystemicdrugabsorptionfromtheGIT
orotherextra-vascularsiteisdependenton
1.thephysicochemicalpropertiesofthedrug,
2.thetypeanddesignofdosageform&
3.theanatomyandphysiologyofthedrug
absorptionsite.

4. •Therateofchangeintheamountofdrug
inthebody(dD
B/dt),dependsonthe
relativeratesofdrugabsorptionand
elimination.
•Thenetrateofdrugaccumulationinthe
bodyatanytimeisequaltotherateof
drugabsorptionminustherateofdrug
elimination,regardlessofwhether
absorptionrateiszeroorderorfirstorder.

6. •D
GI:Theamountofdruginthe
gastrointestinaltract
•D
E:Theamountofdrugeliminated.
•Duringtheabsorptionphaseofa
plasmalevel–timecurvetherateof
drugabsorptionisgreaterthantherate
ofdrugelimination.
•During theabsorption phase,
eliminationoccurswheneverdrugis
presentintheplasma,eventhough
absorptionpredominates.

8. Zero order kinetics
In0orderkineticsaconstantamountof
drugiseliminated/perunittime.
This is a state
atwhichtherateofan
enzymereactionis
independentofthe
concentrationofthe
substrate/drug
administered.
Zero-order process takes
place at a fixed rate,
independent of the
existing concentration/
initial concentration

9. Halflifedependsoninitialdrug
concentration.Atsometime,thezero
orderprocesscomestoanend.E.g.:
IVinfusions,controlled/sustaineddrug
deliverysystems,carrierbased
processesaftersaturation.
Forexample10mgofadrugmaybe
eliminatedperhour,thisrateof
eliminationisconstantandis
independentofthetotaldrug
concentrationinthebody(plasma).

10. To make it seem easier
•Apatientwasgiven100mgofdrugAorally.Assume
thatthedrugabsorptionfollowszero-orderkineticsat
arateof10mg/min.Itmeansforeveryminute,10mg
ofthedrugwillundergoabsorption.
•Itmeansafter6minutes,6x10mg=60mgdrugwill
beabsorbed.
•Similarly80mgwillbeabsorbedafter8minutes.
•Itmeansitwilltake10minutesforcomplete
absorptionofdrugandtheprocesscomestoanend.
•Itmeansineachunittimeafixedamountofdrugwill
beabsorbed,comewhatmay(innormalphysiological
conditions).

11. •First-orderprocesstakesplaceata
constantproportionofthedrug
concentrationavailableatthattimeso
theprocessisdependentontheinitial
concentration.
First order kinetics
•Halflifedoesnotdependonconcentration
andisaconstantvalue.E.g.:absorption,
distribution,metabolismandexcretion(not
linkedwithcarrierorunsaturablestateif
linkedwithcarriers).

12. •Apatientwasgiven100mgofdrugorallyanditwasassumedtobe
followingIorderkineticsthenaproportionof10%perminute,ofthe
existingconcentrationatthattimewillbeabsorbed.
•So,infirstminute10%ofinitialdrugi.e.,10mgwillbeabsorbed.
•Inthesecondminuteagain10%willbeabsorbedbutherethedrug
remainedforabsorption(afterfirstminute)is100-10=90mgonly.So
10%of90mgwillbeabsorbedinthesecondminute.Thenhowmuchit
willbe:9mg.So,attheendofsecondminute,81mgwillberemained
forabsorption.
•Inthirdminuteagain10%,but10%of81mgi.e.,8.1mgwillbe
absorbed.
•Similarlyin4thminute,10%of72.9mgi.e.,7.29mgwillbeabsorbed.
•Aftersometime,if1mgisremainedtobeabsorbed,thenalso10%of
that1mgonlywillbeabsorbed.Thatmeansthefirst-orderprocess
nevercomestoanendsinceittakesplaceatcertainproportionofthe
concentrationexistingatthattime.
To make it seem easier

13. To sum the process, I am using few well
illustrated images from net with
acknowledging their source with.

14. https://i.ytimg.com/vi/XEotDfKhNTw/
maxresdefault.jpg
•Source for last image.

15. Next image shows drug
absorption.

17. https://i.ytimg.com/vi/3Bw6kci87Wk/
maxresdefault.jpg
•Theseimagesexplaintheconceptvery
beautifully,soIamnotwritingevenasingle
wordfrommyside.Thankstooriginal
creator.

18. Next image shows drug
elimination.

19. http://tmedweb.tulane.edu/pharmwik
i/lib/exe/fetch.php/pk.png

20. http://www.themednote.com/wp-
content/gallery/basic-science/pharmacoloy/pharm-
basic/drug-metabolism.jpg

21. What is the trend ?
•Formostsitesofadministrationdrug
absorptionfollowsfirstorderkinetics&
formostroutesofeliminationthe
processalsoisfirstorderor
exponential.

22. sepia.unil.ch/pharmacology/index.php?id=94
95%ofthedrugs(attherapeuticdose)are
eliminatedbyfirstordereliminationkinetics.
A few substances reflectzero-
ordereliminationkineticsastheirelimination
processissaturated.
ExamplesareEthanol,Phenytoin,Salicylates,
Cisplatin,Fluoxetin,Omeprazol.

23. Inpharmacokinetics,theoverallrateof
drugabsorptionmaybedescribedas
eitheraIorderor0orderprocess.
Mostpharmacokineticmodelspresume
first-orderabsorptionunlesszero-order
modelassumptionimprovesthemodel
appreciablyorhasbeenverified
experimentally.

24. Why it is so ?
Formostdrugs,absorptionand
eliminationfollowfirstorderkinetics
becausethedrugconcentrationisnot
sufficienttosaturatethemechanism
forabsorptionorelimination.Ifthe
processsaturates,thenzeroorder
kineticsfitsthemodel.