PharmacokineticsDr. M. Yulis Hamidy, MKes, MPdKed

Definition• Pharmacodynamics = the effects of the drug

on the body

• Pharmacokinetics = the way the body affects the drug with time– absorption– distribution– biotransformation / metabolism– excretion of drugs

Passage of drugs through body• Administration

• Absorption

• Distribution

• Metabolism

• Excretion

Site of drug actionMetabolismliver, GIT, lung

Excretionurine, feaces, expelled air

Storage fat, cytoplasm, bone

Plasma CompartmentBound Free drug drug

Drug Administrationparental, oral, topical

Routes of administration

• Oral• Parental• Topical

– buccal– vaginal– anal– dermal– ocular– nasal

First pass metabolism

• Plasma levels after different routes of administration

Time (hrs)

Plas

ma

conc

entra

tion IV

Oral

Topical

Drug Distribution

• molecular size

• lipophilicity

• plasma binding

• blood flow to different organs

• lean:fat body weight

pKa of drug and pH of environment

distribution

Plasma binding

distribution

Blood Flow

distribution

Drug Biotransformation

• most drugs

• Phase 1

• Phase 2

• ind/inh

• tissues

• prodrugs

Metabolism

Elimination

• First order

• zero order

• intermediate

Pharmacokinetics

• One-compartment model

• Two-compartment model

Steady state concentration

Age, Sex, Race• Age

– infants– children– elderly

• Sex• Race

• pharmacokinetic basis

• pharmacodynamic basis

Drug Interactions

Effect of Disease on Drug Action

• cardiovascular disease• liver function• celiac disease• viral infections• renal disease• asthma• Alzheimer-type dementia

Bioavailability• Bioavailability is defined as the fraction of unchanged

drug reaching the systemic circulation following administration by any route.

• The area under the blood concentration-time curve (area under the curve, AUC) is a common measure of the extent of bioavailability for a drug given by a particular route.

• For an intravenous dose of the drug, bioavailability is assumed to be equal to unity. For a drug administered orally, bioavailability may be less than 100% for two main reasons—incomplete extent of absorption and first-pass elimination.