RELATIONSHIP BETWEEN CYP3A5 GENOTYPES AND EFFECT OF VERAPAMIL ON MIDAZOLAM

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。CYP3A4和CYP3A5是成人肝脏和小肠中含量最多的CYP3A酶，参与50%以上药物的代谢。CYP3A活性的巨大个体间差异极大地影响了CYP3A底物的口服生物利用度和全身清除率的变化。遗传变异是造成个体间变异的主要因素之一。最近，几种常见的CYP3A5基因变异已经被发现，它们决定了CYP3A5的表达水平和活性，并可能决定个体对药物相互作用的易感性。由于维拉帕米对CYP3A4和CYP3A5的抑制存在差异，我们计划研究CYP3A5基因型与维拉帕米介导的药物相互作用之间的关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The CYP3A4 and CYP3A5 are the most abundant CYP3A enzymes in adult human liver and small intestine, and are responsible for metabolism of more than 50% of all drugs. Substantial interindividual differences in CYP3A activity contribute greatly to variation in oral bioavailability and systemic clearance of CYP3A substrates. Genetic variation is one of the major factors that contribute to the interindividual variability. Recently, several common CYP3A5 gene variants, which determine the expression level and activity of CYP3A5, have been identified and could determine individual susceptibility to drug interactions. Since verapamil differentially inhibits CYP3A4 and CYP3A5, we plan to study the association between CYP3A5 genotypes and verapamil-mediated drug interactions.