Insights into CYP2B6-mediated drug–drug interactions

作     者：William D.Hedrich Hazem E.Hassan Hongbing Wang 

作者机构：Department of Pharmaceutical SciencesUniversity of Maryland School of Pharmacy 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2016年第6卷第5期

页      面：413-425页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by research grants from the U.S. National Institute of Health (DK061652 and GM107058) 

主　　题：CYP2B6 CAR PXR Polymorphism Drug–drug interaction Cyclophosphamide Efavirenz 

摘      要：Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously *** discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the *** expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor(CAR) and pregnane X receptor(PXR) in the *** addition to CYP2B6,these receptors also mediate the inductive expression of CYP3A4,and a number of important phase II enzymes and drug ***2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide,anesthetics propofol and ketamine,synthetic opioids pethidine and methadone,and the antiretrovirals nevirapine and efavirenz,among *** inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate *** variances arise from a number of sources including genetic polymorphism,and xenobiotic *** this review,we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.