DETERMINATION OF FIRST PASS INTESTINAL METABOLISM OF MIDAZOLAM IN HUMAN SUBJECTS

咪达唑仑在人体中首过肠道代谢的测定

• 批准号: 6115617
• 负责人: ALASTAIR J. J. WOOD
• 金额: $ 3.64万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6115617
• 关键词: clinical research; cytochrome P450; drug interactions; drug metabolism; enzyme activity; gastrointestinal drug absorption; gastrointestinal pharmacology; human subject; intravenous administration; ketoconazole; midazolam; oral administration; pharmacokinetics

To estimate the intestinal contribution to the first pass metabolism of orally administered midazolam. The hypothesis is that midazolam is metabolized by intestinal cytochrome P450 3 A (P450 3A) enzymes to a clinical significant amount. To measure the effect of P450 3A inhibition by orally administered ketoconazole on the pharmacokinetic parameters of orally and intravenously administered midazolam. The hypothesis is that oral ketoconazole affects the disposition of the oral dose more than that of the intravenous midazolam. Preliminary analysis has shown some racial differences in the metabolism of midazolam. Continued analysis will determine to what extent the significance.

为了估计肠道对首过代谢的贡献， 口服咪唑安定。假设咪达唑仑是 由肠细胞色素P450 3A（P450 3A）酶代谢为 临床显著量。 为了测量P450 3A抑制的效果，通过口服给予 酮康唑对口服给药的药代动力学参数和 静脉注射咪达唑仑假设是口服 酮康唑对口服剂量分布的影响大于 静脉注射咪唑安定初步分析显示， 咪达唑仑代谢的差异。继续分析将 确定其重要性到什么程度。