Cytochrome P450 2B6 and Cytochrome P450 3A4 (CYP2B6, CYP3A4)

Cytochrome P450 2B6 is a liver-expressed monooxygenase enzyme involved in the oxidative metabolism of approximately 2%–10% of clinically used drugs and some endogenous compounds. The enzyme is highly polymorphic, contributing to significant variability in patient drug response, and is induced and regulated by xenobiotic-sensing nuclear receptors such as CAR and PXR. It metabolizes a variety of drugs including antineoplastics, anesthetics, opioids, antiretrovirals, and more, and can be co-regulated with other P450 enzymes, affecting the potential for drug–drug interactions and toxicity. Cytochrome P450 3A4 is the most abundant P450 enzyme in the adult human liver and intestine, responsible for the metabolism of around 50% of clinically used drugs. It acts on a broad spectrum of substrates, catalyzing oxidation, hydroxylation, and epoxidation reactions. CYP3A4's activity is regulated by external compounds and endogenous factors and can be influenced by inducers (e.g., some anticonvulsants, glucocorticoids) or inhibitors (e.g., certain antibiotics, grapefruit juice), making it central to clinically significant drug–drug interactions. Both CYP2B6 and CYP3A4 are often co-induced and co-regulated by nuclear receptors (e.g., CAR and PXR), leading to coordinated changes in metabolism for their shared drug substrates. These enzymes are responsible for much of the observed interindividual differences in drug clearance and are common sites of drug–drug interactions and pharmacogenomic variability.

Other names

CYP2B6CYPIIB6CYP3A4CYPIIIA4

Both enzymes primarily function in drug inactivation (metabolism to less active forms) and drug activation (bioactivation of prodrugs). They catalyze oxidation and monooxygenase reactions of a broad spectrum of substrates, and CYP3A4 also exhibits epoxygenase activity, metabolizing arachidonic acid to EETs and other signaling molecules. They are involved in metabolic activation/detoxification of xenobiotics.