CYP3A4

If the cytochrome P450 family is a factory, CYP3A4 is its busiest assembly line. It is the single most abundant P450 in the human liver and intestine, and it has an unusually roomy active site, so it can accept and metabolize an enormous variety of drugs — by many estimates, roughly half of all medications on the market.

CYP3A4 carries out oxidative phase I reactions on substrates ranging from statins and calcium channel blockers to many immunosuppressants, opioids, and antifungals. Its heavy presence in the gut wall also makes it a major contributor to the first-pass effect of orally taken drugs.

Because so much traffic passes through this one enzyme, CYP3A4 is a notorious hub for drug interactions. Inhibitors such as ketoconazole or grapefruit juice can sharply raise the levels of a co-administered substrate, while inducers such as rifampicin or St John's wort can render it ineffective. Unlike some other P450s, common CYP3A4 activity differences are driven more by these environmental factors than by a single strong genetic polymorphism.