CYP2B6

CYP2B6 is a member of the cytochrome P450 superfamily of enzymes that catalyze the oxidation of a wide range of endogenous and exogenous compounds. In humans, the enzyme is primarily expressed in the liver, with detectable levels in other tissues such as the brain and kidneys. The protein is encoded by the CYP2B6 gene and participates in Phase I drug metabolism, introducing oxygen into substrates to facilitate further processing and elimination.

CYP2B6 metabolizes a variety of clinically important drugs and xenobiotics. Notable substrates include antiretroviral drugs such as efavirenz, the antidepressant and smoking cessation agent bupropion, and the chemotherapeutic prodrugs cyclophosphamide and ifosfamide. It also participates in the metabolism of several other medications with narrow therapeutic windows, contributing to both activation and detoxification pathways.

Genetic variation in CYP2B6 is common and leads to substantial interindividual differences in enzyme activity and drug exposure. Specific alleles can reduce or alter catalytic activity, which can cause higher plasma levels and modified responses for susceptible drugs. The CYP2B6*6 variant is frequently studied and is associated with reduced metabolic capacity for several substrates, notably efavirenz. Population frequencies of functionally important variants vary across ethnic groups and can influence dosing considerations.

CYP2B6 expression and activity can be influenced by drug interactions and regulatory factors. Inducers can increase metabolism, while inhibitors can decrease it, affecting drug concentrations and the risk of adverse effects. Understanding CYP2B6 genotype and activity is increasingly used to guide dosing for certain medications, particularly in HIV therapy and oncology.