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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 CYP3A 在体外代谢美沙酮，多年来人们一直认为 CYP3A 负责人体美沙酮体内代谢和处置。 然而，现在很清楚，人类美沙酮的处置不受 CYP3A 活性的控制。 负责人美沙酮体内清除和处置的主要 CYP 仍有待确定。 CYP2B6 是体内美沙酮代谢的主要决定因素，间接证据表明 CYP2B6 在体内发挥作用。 这项研究将检验以下假设：CYP2B6 是负责人美沙酮 N-去甲基化、动力学和人体体内临床效果的主要酶。 对健康志愿者的交叉研究将评估在不存在或存在噻氯匹定（人类 CYP2B6 活性的选择性抑制剂）的情况下美沙酮的代谢和处置。