CYP2B6 is a member of the cytochrome P450 family of important pharmacogenes and makes up approximately 2–10% of the total hepatic CYP content . CYP2B6 is also expressed in the brain, and may be an important factor in the metabolism of drugs acting on the central nervous system (CNS) and neurological side effects of drug treatments . CYP2B6 is responsible for the metabolism of 4% of the top 200 drugs  and is highly inducible by several drugs and other xenobiotics . There is high interindividual variation in CYP2B6 mRNA expression, ranging from 20 to 250-fold, which may be attributed to differential transcriptisonal regulation and inherited genetic variation [4–6]. A large number of variants have been reported (see the CYP allele nomenclature committee website http://www.cypalleles.ki.se/cyp2b6.htm), including many that are present at high frequencies and several that show linkage resulting in multiple haplotypes. These haplotypes are often observed at highly different frequencies in different racial and ethnic groups (reviewed in ). CYP2B6 has been shown to undergo significant alternative splicing . Although multiple splice variants of CYP2B6 have been reported, the functional relevance of most of these needs further investigation. One of the splice variants, SV1, has been shown to be linked to an important variant (see below for more details) [6,8]. Like other CYPs, CYP2B6 has a high level of homology with a pseudogene, CYP2B7P1, which can interfere with genotyping if assays are not specific enough .
Transcription of CYP2B6 is regulated by the nuclear receptors PXR and CAR, coded for by the genes NR1I2 and NR1I3, respectively. They activate transcription by binding at the proximal response element (PREM located at −1.7 kb upstream of the transcription start site) and the distal response element (XREM located at −8.5 kb of the transcription start site) [9,10] in the CYP2B6 promoter. Cross-regulation between CYP2B6 and CYP3A4, UGT1A1 and hepatic drug transporters that are also regulated by these common transcription factors has been suggested . Many of the drugs that are metabolized by CYP2B6 are also inducers of the gene (through PXR and CAR), including cyclophosphamide, phenobarbital, rifampicin, phenytoin, artimesin, carbamazepine, efavirenz, and nevirapine  (see http://www.pharmgkb.org/search/annotatedGene/cyp2b6/index.jsp for a larger list of substrates, inhibitors, and inducers of CYP2B6). Although sex has also been shown to influence CYP2B6 expression, there have been conflicting reports in the literature, which may in turn be because of confounding factors such as race and environment (discussed in Ref. ).
As CYP2B6 is the major enzyme involved in the metabolism of efavirenz and nevirapine, its pharmacogenomics has become relevant for the treatment of HIV. Efavirenz has a narrow therapeutic window with severe CNS side effects associated with its high plasma concentrations and treatment failure associated with low concentrations. The variants CYP2B6:516G > T and CYP2B6:983T > C, as well as the haplotype CYP2B6*6 have been associated with adverse effects of efavirenz treatment (discussed below in more detail). Clinical significance of CYP2B6 variants has also been implicated in cyclophosphamide chemotherapy [11,12] and in smoking cessation in response to bupropion [13–16].