CYP2B6 ACTIVITY AND DRUG EFFECTS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 CYP 3A在体外代谢美沙酮，并且多年来假定CYP 3A负责人美沙酮在体内的代谢和处置。 然而，现在清楚的是，人类美沙酮处置不受CYP 3A活性。 负责人美沙酮清除和体内处置的主要代谢物仍有待确定。 CYP 2B 6是体内美沙酮代谢的主要决定因素，间接证据表明CYP 2B 6在体内发挥作用。 本研究将检验以下假设：CYP 2B 6是人体内负责人美沙酮N-去甲基化、动力学和临床效应的主要酶。 在健康志愿者中进行的交叉研究将评价在不存在和存在噻氯匹定（一种人CYP 2B 6活性的选择性抑制剂）的情况下美沙酮的代谢和处置。

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. CYP3A metabolizes methadone in vitro, and for many years it was assumed that CYP3A was responsible for human methadone metabolism and disposition in vivo. However, it is now clear that human methadone disposition is not governed by CYP3A activity. The predominant CYP responsible for human methadone clearance and disposition in vivo remains to be identified. CYP2B6 is a major determinant of methadone metabolism in vivo, and indirect evidence suggests a role for CYP2B6 in vivo. This investigation will test the hypothesis that CYP2B6 is a predominant enzyme responsible for human methadone N-demethylation, kinetics and clinical effects in humans in vivo. A crossover investigation in healthy volunteers will evaluate the metabolism and disposition of methadone in the absence and presence of ticlopidine, a selective inhibitor of human CYP2B6 activity.