Cytochrome P450 enzymes - Drug Interactions

}  Cytochrome P450 (CYP) is a family of isoenzymes responsible for the oxidation of organic substances.

}  Most of the oxidative reactions of drugs are performed by six main enzymes:

v CYP 1A2

v CYP 2C9

v CYP 2C19

v CYP 2D6

v CYP 2E1

v CYP 3A4

}  Enzyme induction:

v The main drugs responsible for induction of the most clinically important cytochrome P450 isoenzymes are Griseofulvin, Phenytoin, Rifampicin, St. John’s wort, Carbamazepine, Phenobarbitone and Cigerette Smoke.

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v CYP 1A2 is induced by tobacco smoke (Smoking)

v CYP2E1 is induced by alcohol consumption.

}  Enzyme inhibition:

v The main drugs responsible for inhibition of the most clinically important cytochrome P450 isoenzymes are Sulphonamides, Antifungals ( Itraconazole, Ketoconazole, Fluconazole), Macrolide Antibiotics (Clarithromycin, Azithromycin, Erythromycin), Ciprofloxacin, Sertraline, Cimetidine, Omeprazole, Metronidazole, Antivirals (Ritonavir, Indinavir, Nelfinavir, Amprenavir), Antiarrhythmics (Amiodarone, Quinidine), Antidepressants (Fluoxetine, Paroxetine), Isoniazid and Alcohol.

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}  Understanding the mechanism underlying drug interactions helps to prevent drug toxicity or adverse effects.

}  Prediction of drug interactions in advance may reduce the number of expensive clinical studies.