EFFECT OF DMP 266 ON HEPATIC AND INTESTINAL CYP3A ACTIVITY

DMP 266 对肝脏和肠道 CYP3A 活性的影响

• 批准号: 6274716
• 负责人: KENNETH S LOWN
• 金额: $ 2.15万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6274716
• 关键词: biopsy; clinical research; dosage; drug metabolism; drug screening /evaluation; enzyme activity; erythromycin; gastrointestinal absorption /transport; human subject; intravenous administration; liver metabolism; oral administration; oxygenases; pharmacokinetics; volunteer

In animal studies, DMP 266 has been demonstrated to induce its own metabolism and increase hepatic CYP3A and CYP2B enzyme activities. In humans, CYP3A4 is the predominant phase-I metabolizing enzyme present in the liver and intestine, and the available data suggest that it may be induced by DMP 266. To definitively determine if this is the case, 24 healthy volunteers will be randomized to receive either DMP 266 (200 mg or 400 mg/daily) or placebo orally for 10 days. Intestinal biopsies will be obtained prior to the first dose of DMP 266 and on the day after administration of the 10th dose. In addition, single intravenous doses of [14-C-N-methyl] erhthromycin will be administered on 9 different occasions throughout the study.

在动物实验中，DMP 266已被证明可以诱导其自身 代谢，提高肝脏细胞色素P3A和细胞色素P450 B酶活性。在……里面 人类，CYP3A4是目前存在的主要的I相代谢酶 在肝脏和肠道中，而现有的数据表明，它可能 由DMP 266诱导。为了最终确定情况是否如此， 24名健康志愿者将被随机接受DMP 266(200 每日服用400毫克)或服用安慰剂10天。肠道活组织检查 将在第一剂DMP 266之前和第二天获得 第10剂给药。此外，单次静脉注射剂量 的[14-C-N-甲基]红霉素将在9个不同的 在整个研究过程中的各种场合。