CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme.

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Wang H, Tompkins LM

CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme.

Curr Drug Metab. 2008 Sep;9(7):598-610.

PubMed ID

18781911 [ View in PubMed

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Abstract

Human CYP2B6 has been thought to account for a minor portion (<1%) of total hepatic cytochrome P450 (CYP) content and to have a minor function in human drug metabolism. Recent studies, however, indicate that the average relative contribution of CYP2B6 to total hepatic CYP content ranges from 2% to 10%. An increased interest in CYP2B6 research has been stimulated by the identification of an ever-increasing substrate list for this enzyme, polymorphic and ethnic variations in expression levels, and evidence for cross-regulation with CYP3A4, UGT1A1 and several hepatic drug transporters by the nuclear receptors pregnane X receptor and constitutive androstane receptor. Moreover, 20- to 250-fold interindividual variation in CYP2B6 expression has been demonstrated, presumably due to transcriptional regulation and polymorphisms. These individual differences may result in variable systemic exposure to drugs metabolized by CYP2B6, including the antineoplastics cyclophosphamide and ifosfamide, the antiretrovirals nevirapine and efavirenz, the anesthetics propofol and ketamine, the synthetic opioid methadone, and the anti-Parkinsonian selegiline. The potential clinical significance of CYP2B6 further enforces the need for a comprehensive review of this xenobiotic metabolizing enzyme. This communication summarizes recent advances in our understanding of this traditionally neglected enzyme and provides an overall picture of CYP2B6 with respect to expression, localization, substrate-specificity, inhibition, regulation, polymorphisms and clinical significance. Emphasis is given to nuclear receptor mediated transcriptional regulation, genetic polymorphisms, and their clinical significance.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Cyclophosphamide	Cytochrome P450 2B6	Protein	Humans	Unknown	Substrate Inducer	Details
Dexamethasone	Cytochrome P450 2B6	Protein	Humans	Unknown	Inducer	Details
Dexamethasone acetate	Cytochrome P450 2B6	Protein	Humans	Unknown	Inducer	Details