• Also referred to as “Biotransformation”.
  • Primary site: Liver.


  • Non-synthetic/phase I/functionalization reactions:
  • Functional group is generated or exposed-metabolite may be active or inactive.

Synthetic/phase II reactions/conjugation:

  • Metabolite is mostly inactive.
  • Exceptions e.g. Glucuronide conjugate of morphine & sulfate conjugate of minoxidil are active.

Steps for biotransformation:

  • May occur with help of microsomal or non-microsomal enzymes.
  • Microsomal enzymes present in smooth endoplasmic reticulum.
  • Eg of microsomal enzymes: Cytochrome P-450, UGTs.
  • Results in increased metabolic rate of inducing drug itself or other drugs.
  • Inducers are relatively selective for certain isoenzyme families.

Microsomal enzyme induction:

  • Drugs induce microsomal enzymes & hence, drug metabolism induced.
  • Eg:

CYP3A isoenzyme inducer:

  • Anticonvulsants (phenobarbitone, phenytoin, carbamazepine), rifampin, glucocorticoids.

CYP2B1 inducer:

  • Phenobarbitone.

CYP2D6 inducer:

  • Rifampin.

CYP2E1 inducer:

  • Isoniazid & chronic alcohol consumption.

CYP1A inducer:

  • Polycyclic hydrocarbons like 3-methylcholanthrene and benzopyrene found in cigarette smoke, charcoal, broiled meat, omeprazole & industrial pollutants.

Other important enzyme inducers:

  • Phenylbutazone, griseofulvin, DDT.

Drug-to-drug interaction by enzyme induction:

1. Drugs enhancing drug metabolism in humans:

Inducing drug Drug with enhanced metabolism
Benzoapyrene Theophylline
Chlorcyclizine Steroid hormones
Ethchlorvynol Warfarin
Glutethimide Antipyrine, glutethimide, warfarin
Griseofulvin Warfarin

(except secobarbital)

Barbiturates, chloramphenicol, chlorpromazine, cortisol, coumarin anticoagulants, desmethylimipramine, digitoxin, doxorubicin, estradiol, phenylbutazone, phenytoin, quinine, testosterone
Phenylbutazone Aminopyrine, cortisol, digitoxin
Phenytoin Cortisol, dexamethasone, digitoxin, theophylline
Rifampin Coumarin anticoagulants, digitoxin, glucocorticoids, methadone, metoprolol, oral contraceptives, prednisone, propranolol, quinidine

2. Drug inhibiting drug metabolism in humans:


Drug whose metabolism is inhibited
Allopurinol, Isoniazid


Antipyrine, dicumarol, probenecid, tolbutamide
Cimetidine Chlordiazepoxide, diazepam, warfarin, others
Dicumarol Phenytoin
Diethylpentenamide Diethylpentenamide
Disulfiram Antipyrine, ethanol, phenytoin, warfarin
Ethanol Chlordiazepoxide, diazepam, methanol
Grapefruit juice Alprazolam, atorvastatin,cisapride, cyclosporine, midazotam,Triazolam
Ketoconazole Cyclosporine, astemizole, terfenadine
Nortriptyline, Oral contraceptives Antipyrine
Phenylbutazone Phenytoin, tolbutamide
Secobarbital Secobarbital
Troleandomycin Theophylline, methylprednisolone

Exam Important

  • Non-synthetic is also referred to as “phase I/functionalization reactions”.
  • Synthetic is also referred to as “phase II/conjugation reactions”.
  • Glucuronide conjugate of morphine & sulfate conjugate of minoxidil is active.
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