Metabolism &

Excretion
Dr. Anant Khot

Biotransformation reactions
Reactions
Oxidation
Reduction

Examples of drugs
Phenytoin, Diazepam,
Ibuprofen
Halothane

Hydrolysis

Pethidine, Procaine

Glucuronide conjugation

Morphine, Bilirubin

Acetylation

Sulfonamides, Isoniazid

Methylation
Glutathione conjugation

Histamine, captopril
Paracetamol

Isoenzyme
P450

Drug(s)

CYP1A2

Caffeine, paracetamol, tacrine, theophylline

CYP2B6

Cyclophosphamide, methadone

CYP2C8

Paclitaxel, repaglinide

CYP2C19

Omeprazole, phenytoin

CYP2C9
CYP2D6

Ibuprofen, tolbutamide, warfarin

Codeine, debrisoquine, S-metoprolol

CYP2E1

Alcohol, paracetamol

CYP3A4, 5, 7

Ciclosporin, nifedipine, indinavir, simvastatin

ENZYME INDUCTION
Process speeds up the biotransformation of the
inducing drug itself and other drugs
metabolized by the microsomal enzymes

Consequences- Variable response & result in

disease

Drug interactions { Therapeutic failure, drug

toxicity}

Tolerance to drugs
Use: Phenobarbitone- use in newborn jaundice

Enzyme inhibition
Drugs inhibit cytochrome P450 enzyme
activity

Competitively inhibit the metabolism of

endogenous substances like testosterone
and other drugs given concurrently.

Consequences: Toxicity
PK enhancer- Ritonavir boosted Lopinavir