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Pharmacogenomics. 2007 Jul;8(7):743-59.

Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance.

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Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D-70376 Stuttgart, Germany.


Polymorphisms in drug-metabolizing enzymes and drug transporters contribute to wide and inheritable variability in drug pharmacokinetics, response and toxicity. One of the less well-studied human cytochrome P450s is (CYP)2B6, a homologue of the rodent phenobarbital-inducible CYP2B enzymes. Clinically used drug substrates include cytostatics (cyclophosphamide), HIV drugs (efavirenz and nevirapine), antidepressants (bupropion), antimalarials (artemisinin), anesthetics (propofol) and synthetic opioids (methadone). Contrary to the model polymorphisms of CYP2D6 and CYP2C19, which were discovered by adverse drug reactions, pharmacogenetic study of CYP2B6 was initiated by reverse genetics approaches and subsequent functional and clinical studies. With over 100 described SNPs, numerous complex haplotypes and distinct ethnic frequencies, CYP2B6 is one of the most polymorphic CYP genes in humans. In this review, we summarize general biomolecular and pharmacological features and present a detailed up-to-date description of genetic polymorphisms, including a discussion of recent clinical applications of CYP2B6 pharmacogenetics.

[Indexed for MEDLINE]

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