CYP3A4entsyymin

CYP3A4 is a member of the cytochrome P450 superfamily of enzymes and is encoded by the CYP3A4 gene. It functions as a heme-containing monooxygenase that catalyzes the oxidation of a wide range of substrates, including many drugs, steroids, and other endogenous compounds. It is highly expressed in the liver and small intestine, where it contributes substantially to first-pass metabolism and systemic clearance of xenobiotics.

CYP3A4 has broad substrate specificity and high catalytic efficiency, often able to metabolize chemically diverse compounds. It commonly generates multiple metabolites per substrate, and its activity can be influenced by physiological conditions and co-medications. Due to its broad role, CYP3A4 is a central player in numerous drug disposition pathways.

Regulation of CYP3A4 expression is dynamic. It is inducible via nuclear receptors such as pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in response to inducers like rifampin and phenobarbital. It can be inhibited by several drugs and dietary components, notably certain azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (erythromycin), and grapefruit juice, which reduces intestinal metabolism and increases drug exposure.

Clinical significance: Interindividual variability in CYP3A4 activity affects the pharmacokinetics of many medications, contributing to differences in efficacy and risk of adverse effects. Genetic polymorphisms, such as CYP3A4*22, can decrease hepatic activity, while others show variable effects. Drug interactions through induction or inhibition of CYP3A4 are common considerations in dose adjustment and safety monitoring.