Clinical Assessment of Herb-Drug Interactions

草药-药物相互作用的临床评估

• 批准号: 6803077
• 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 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6803077
• 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酶和/或多药排出泵P-糖蛋白的诱导或抑制引起的药物与药物的不良相互作用是公认的。随着草药膳食补充剂的广泛使用，草药与药物相互作用的潜力正在成为一个重要的医学问题。最近的调查表明，4500万美国人经常使用草药疗法，近五分之一的服用处方药的人也在服用草药补充剂。这意味着超过1500万成年人在服用草药补充剂的同时服用处方药。此外，据指出，70%的患者没有向初级保健提供者透露他们的草药使用情况。因此，潜在的草药与药物相互作用的风险是相当大的。医学文献中有记载的草药-药物相互作用的报道。虽然一些体内研究表明，植物药的植物化学成分可以调节肝脏药物代谢酶(细胞色素P-450s，CYP)和多药外排泵P-糖蛋白(P-gp)，但尚未有前瞻性的体内研究评估草药与药物的相互作用及其潜在的机制。需要检验的假设是，同时使用草药膳食补充剂和传统药物可以引起草药与药物的相互作用，继而发生草药介导的药物吸收和消除的变化。目前的建议将评估表型探针药物的口服表观清除量的变化，作为评估长期补充草药对人体肝脏和肠道CYP和/或P-gp活性的影响的一种手段。该项目的目标是：(1)评估美国最畅销的10种草药中，哪些(如果有的话)对CYP介导的和/或P-gp介导的草药-药物相互作用构成风险；(2)确定长期服用Berba|补充剂是否调节特定的CYP活性(即CYPIA2、CYP2D6和CYP3A4)；以及(3)长期使用草药是否可以调节P-gp介导的药物吸收和消除。