Gene Description
CYP2B6
CYP2B6 is a member of the hepatic cytochrome P450 family of important pharmacogenes. It plays important roles in the metabolism of efavirenz, bupropion, and cyclophosphamide1. Clinical Pharmacogenetic Implementation Consortium (CPIC) has issued guidelines for efavirenz dosing based on CYP2B6 genotypes2.
Efavirenz
Efavirenz is the human immunodeficiency virus (HIV) type-1 non-nucleoside reverse transcriptase inhibitor, widely used to treat HIV-1 infection. Substantial evidence demonstrates the association of CYP2B6 genotypes with variability in plasma efavirenz concentrations and with adverse effects1. The CPIC guideline recommends decreased dose to CYP2B6 intermediate metabolizers (IMs) and poor metabolizers (PMs), as these patients may experience higher dose-adjusted trough concentrations compared to normal metabolizers (NMs) and have increased risk of adverse effects. The current data available shows that the effects of the increased function alleles appear to be modest. The guideline therefore recommends standard dosing of rapid metabolizers (RM) and ultrarapid metabolizers (UMs)2. The CPIC guideline also gives specific dosing recommendations to the pediatric patients at different age group and weight groups. Please refer to the guideline for more details.
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References
- Thorn, C.L. et al., PharmGKB summary: very important pharmacogene information for CYP2B6. Pharmacogenetics and genomics. 2010
- Desta, Z., et al., Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-Containing Antiretroviral Therapy. Clin Pharmacol Ther 2019 April [Epub ahead of print]