Actions of a drug on the body.

( Pharmacodynamics )

Body /
Drug Living
system

Actions of the body on the drugs

( Pharmacokinetics )
 Drugs

( Pharmacokinetics ) Absorption

Systemic circulation

Free drug Protein bound drug

Distribution Site of action

(Pharmacodynamics)

Biotransformation

Excretion
 Absorption
Passive difusion (lipid difusion)
Filtration (aqueous difusion)
Active Transport
Passive difusion

Endocytosis
Filtration

Transport
active C
 Drug Administration
Oral
Intravenous
Intramuscular
Subcutaneous
Sublingual
Rectal
Inhalation
Topical
Transdermal
 passive difusion
(lipid difusion)

Degree of acidity
Degree of ionized
Lipid solubility
50 % ionized
pKa drug 3,5 dl. pH 3,5
50 % unionized

9 % ionized
dl. pH 2,5
91 % unionized
 pasive lipid diffusion absorption
Weak acid drugs

In basic medium In acid medium

More ionized, less unionized More unionized, less ionized

Water soluble lipid soluble

Difficult to absorb Easy to absorb

Percentage of ionized

For weak acid

100
% ionized= -----------------
1 + antilog (pKa-pH)

For weak base

100
% ionized= -----------------
1 + antilog (pH-pKa)
example

Aspirin : pKa 3,5

pH stomach 2,5
How many % ionized in the stomach ?
Distribution :

Size of the organ

Blood flow to organ

Solubility

Protein binding Warfarin Plasma albumin

Chloroquin Tissue protein

Amount of drug in the body

Vd =
Conc. Of drug in blood
 Biotransformation process
Polarization
lipid soluble -------- water soluble
Deactivation
most of active drug -------- inactive
Activation
prodrug --------active drug
 Biotransformation
water soluble drug

lipid soluble drug

liver
intestine
excretion
Metabolism/ biotransformation

Phase I reaction / Asyntetic

Oxidation (cytochroom P450)
Reduction
Deamination
Hydrolysis

Phase II reaction ( syntetic ) conjugation

Glucuronate
Acetate
Glutathione
Glycine
Sulphate
Methyl group
Factors that affect metabolism

First pass effect

Enzyme Inducers
Enzyme Inhibitor
 First pass effect / First pass elimination

Systemic circulation

liver
Drugs

Drugs + metabolites
 Enzyme induction / Enzyme inducer

o Barbiturate :Barbiturate
(phenobarbital) Coumarin
Pill contraception
o Phenytoin : Dexamethasone
Pill contraception
o Merokok : Nicotine
(Nicotine ) Pill contraception
Theophyllin
o Rifampicin : Pill contraception
o Carbamazepine: Warfarin
 Enzyme Inhibitor / inhibisi enzim
o Chloramphenicol Phenytoin
Tolbutamide

o Cimetidine Chlordiazepoxide
Diazepam
Chlorazepate
Phenytoin
Theophyllin
o Ketokonazole
o Grapefruit juice
o Ritonavir
 Bioavailability
The fraction of administered dose of drug that
reaches the systemic circulation
Bioavailability of intravenous administration is
100%
Bioavailability of oral administration is reduced
by: destroy by stomach acid, incomplete abs,
expulsion by P-glycoprotein, first pass metabolism
Excretion of drugs

Renal
GI tract
Lung
Sweat
Tear
Breast milk
 Renal excretion

Glomerular Filtration

Tubular active secretion

Reabsorption

Excretion