CYP2B6 ACTIVITY AND DRUG EFFECTS

CYP2B6 活性和药物作用

• 批准号: 7603378
• 负责人: Evan D. Kharasch
• 金额: $ 0.15万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603378
• 关键词: CYP2B6 gene; CYP3A4 gene; Computer Retrieval of Information on Scientific Projects Database; Enzymes; Funding; Grant; Human; In Vitro; Institution; Investigation; Kinetics; Metabolism; Methadone; Pharmaceutical Preparations; Research; Research Personnel; Resources; Role; Source; Testing; Ticlopidine; United States National Institutes of Health; clinical effect; cytochrome P450 3A; demethylation; healthy volunteer; in vivo; inhibitor/antagonist

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 CYP3A在体外代谢美沙酮，多年来，人们认为CYP3A负责人类美沙酮代谢和体内处置。 但是，现在很明显，人类美沙酮处置不受CYP3A活性的控制。 负责人类美沙酮清除和体内处置的主要CYP仍有待鉴定。 CYP2B6是美沙酮代谢体内的主要决定因素，间接证据表明在体内CYP2B6起作用。 该研究将检验以下假设：CYP2B6是负责人类美沙酮N-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跨界调查将在不存在和存在Ticlopidine（人类CYP2B6活性的选择性抑制剂）的情况下评估美沙酮的代谢和处置。