The role of CYP 2B6 in Drug Metabolism
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1
University of Belgrade, Department of Pharmacology, Serbia
Cytochrome P450 (CYP2B6) is mainly expressed in the liver. In the past it has been thought that CYP2B6 accounts for less than 1% of total hepatic CYP450 content and that 3% of drugs are metabolized by CYP2B6. However, recent studies demonstrated that the average contribution of CYP2B6 to total hepatic CYP 450 content ranges from 2-10%, while CYP2B6 is involved in metabolism of approximately 8% of clinically used drugs (n>60). CYP2B6 is also expressed in brain. That may be of relevance for the metabolism of CNS-acting drugs and neurological side effects of drugs. Clinically used drugs that are substrates for CYP2B6 include: the cytostatics (cyclophosphamide, ifosfamide, and tamoxifen), the antiretrovirals (efavirenz and nevirapine), the antidepressants (bupropion), the antimalarials (artemisinin), the anesthetics (propofol and ketamine), the synthetic opioide methadone, the anti-parkinsonian selegiline and appetite suppressant sibutramine. CYP2B6 is involved in bioactivation of several procarcinogens and toxicants.
CYP2B6 is a highly inducible enzyme. Some of the CYP2B6 inducers are also have been shown to induce CYP3A4, CYP2C19, UGT1A1 and MDR1 (phenobarbital, rifampin, phenytoin, carbamazepine and clotrimazole). Among CYP2B6 inducers, there are drugs that are also substrates for CYP2B6 and therefore accelerate their own metabolism (cyclophosphamide, ifosfamide, efavirenz and artemisinin). On the other side, rifampin increases the metabolism of co-administered drugs without significantly affecting their own biotransformation.
So far, 29 allelic variants of CYP2B6 (CYP2B6*1 – CYP2B* 29) have been characterized, over 50 haplotypes determined and more than 100 single nucleotide polymorphisms (SNPs) described. Clinical significance of CYP2B6 variants is relevant for the treatment of HIV, cyclophosphamide therapy and smoking cessation in response to bupropion. Novel findings indicate that race/ ethnicity should be considered when dosing drugs that are substrate for CYP2B6.
This communication summarizes recent knowledge related to CYP2B6 expression, substrate-specificity, inhibition, polymorphism and clinical significance.
Keywords:
drug metabolism,
CYP 2B6,
cytochrome P450
Conference:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.
Presentation Type:
Poster
Topic:
Xenobiotic metabolism
Citation:
Ilic
K
(2010). The role of CYP 2B6 in Drug Metabolism.
Front. Pharmacol.
Conference Abstract:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010.
doi: 10.3389/conf.fphar.2010.60.00129
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Received:
05 Mar 2011;
Published Online:
04 Nov 2010.
*
Correspondence:
Dr. Katarina Ilic, University of Belgrade, Department of Pharmacology, Belgrade, Serbia, katarina.v.ilic@gmail.com