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（由申请方提供）：由于诱导或抑制细胞色素P-450酶和/或多药外排泵、P-糖蛋白而引起的药物间不良相互作用已得到充分认可。随着草药膳食补充剂的广泛使用，草药-药物相互作用的可能性正在成为一个重要的医学问题。最近的调查表明，4500万美国人经常使用草药，近五分之一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，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，潜在的草药相互作用的风险是相当大的。在医学文献中报告了记录在案的草药-药物相互作用。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-450，CYP 1A 1）和多药外排泵，P-糖蛋白（P-gp），没有前瞻性的体内研究评估草药-药物相互作用或其潜在的机制已在人类中进行。待检验的假设是，同时使用草药膳食补充剂和常规药物可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炎症和/或P-gp活性的影响的一种手段。本项目的目的是：（1）评估美国10种最畅销的草药中哪些（如果有的话）会对CYP介导和/或P-gp介导的草药-药物相互作用造成风险;（2）确定是否存在长期的小檗碱依赖性。|补充剂的使用调节特定的Pgp活性（即CYPIA 2、CYP 2D 6和CYP 3A 4）;和（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。