Clinical Assessment of Herb-Drug Interactions

草药-药物相互作用的临床评估

• 批准号: 6941693
• 负责人: Bill Gurley
• 金额: $ 30.53万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6941693
• 关键词: P glycoprotein; alternative medicine; blood tests; clinical research; cytochrome P450; dietary supplements; drug interactions; drug metabolism; gastrointestinal drug absorption; human subject; liver metabolism; medicinal plants; urinalysis

DESCRIPTION (provided by applicant): Adverse drug-drug interactions stemming from the induction or inhibition of cytochrome P-450 enzymes and/or the multidrug efftux pump, P-glycoprotein, are well recognized. With the widespread use of herbal dietary supplements, the potential for herb-drug interactions is emerging as a significant medical concern. Recent surveys indicate that 45 million Americans use herbal remedies regularly and that nearly 1 in 5 individuals taking prescription medications are also taking herbal supplements. This translates into more than 15 million adults taking prescription medications concurrently with herbal supplements. Furthermore, it has been noted that 70% of patients do not reveal their herb use to primary care providers. The risk of potential herb-drug interactions, therefore, is considerable. Documented herb-drug interactions are being reported in the medical literature. While a few in vivo studies indicate that the phytochemical components of botanical medicines can modulate hepatic drug metabolizing enzymes (cytochrome P-450s, CYP), and the multidrug efflux pump, P-glycoprotein (P-gp), no prospective in vivo studies assessing herb-drug interactions or their underlying mechanisms have been conducted in humans. The hypothesis to be tested is that concomitant use of herbal dietary supplements and conventional medications can elicit herb-drug interactions secondary to herb-mediated changes in drug absorption and elimination. The current proposal will evaluate changes in apparent oral clearance of phenotypic probe drugs as a means of assessing the effect of prolonged herbal supplementation on hepatic and intestinal CYP and/or P-gp activity in humans. The goals of this project are: (1) to assess which, if any, of 10 top-selling herbs in the United States pose a risk for CYP-mediated and/or P-gp-mediated herb-drug interactions; (2) to determine if prolonged berba| supplement use modulates specific CYP activities (i.e. CYPIA2, CYP2D6 and CYP3A4); and (3) whether prolonged herb use can modulate P-gp-mediated drug absorption and elimination.

描述（由申请人提供）：由细胞色素P-450酶的诱导或抑制和/或多药外排泵p -糖蛋白引起的不良药物-药物相互作用是公认的。随着草药膳食补充剂的广泛使用，草药与药物相互作用的可能性正在成为一个重要的医学问题。最近的调查显示，4500万美国人定期使用草药，近五分之一的服用处方药的人也服用草药补充剂。这意味着超过1500万成年人同时服用处方药和草药补充剂。此外，已经注意到，70%的患者不透露他们的草药使用初级保健提供者。因此，潜在的草药相互作用的风险是相当大的。医学文献中有文献记载的草药相互作用。虽然一些体内研究表明，植物性药物的植物化学成分可以调节肝脏药物代谢酶（细胞色素p -450， CYP）和多药外排泵p -糖蛋白（P-gp），但尚未在人体中进行评估草药相互作用或其潜在机制的前瞻性体内研究。要测试的假设是，同时使用草药膳食补充剂和传统药物可以引起继发于草药介导的药物吸收和消除变化的草药-药物相互作用。目前的提案将评估表型探针药物的表观口服清除率的变化，作为评估长期草药补充对人类肝脏和肠道CYP和/或P-gp活性的影响的手段。该项目的目标是：(1)评估美国10种最畅销的草药中哪一种（如果有的话）会造成cypp介导和/或p- gp介导的草药相互作用的风险；(2)确定长期服用黄连素是否会调节特定的CYP活性（即CYPIA2、CYP2D6和CYP3A4）；(3)长期服用中药是否能调节p- gp介导的药物吸收和消除。