Curcumin-piperine interaction with CYP3A, UGT, and SULT enzymes.

姜黄素-胡椒碱与 CYP3A、UGT 和 SULT 酶的相互作用。

• 批准号: 7220182
• 负责人: Laurie Pauline Volak
• 金额: $ 2.6万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2009-09-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7220182
• 关键词: acetaminophen; clinical research; drug interactions; enzymes; human; liver; metabolism; microsomes; pharmacokinetics

DESCRIPTION (provided by applicant): The use of complementary and alternative medicines has increased dramatically over the past decade as the benefits of these natural medications are realized. Although herbal medicines are commonly believed to be a safer alternative to traditional medications, physicians are increasingly concerned about interactions between these medications. One reason for this concern is that unlike traditional medications, safety and drug interaction data is not required by the FDA prior to the sale of herbal supplements to consumers. Often, such interactions are only discovered after a serious and sometimes life-threatening event has occurred. Curcumin, an herbal supplement of recent clinical interest, is in clinical trials for the treatment of several advanced cancers and Alzheimer's disease. However, limited data has been generated examining curcumin's potential for drug-herb interactions due to inhibition of the major drug metabolizing enzymes. Prior to the broader therapeutic application of curcumin, curcumin's potential for these drug-herb interactions should be investigated. Here, we propose to test the effect of curcumin on the in vitro metabolism of midazolam and acetaminophen, index substrates for phase I (cytochrome P450 isoform CYP3A) and phase II (UDP-glucuronosyltransferase and sulfotransferase) drug metabolism, respectively. Curcumin, due to its limited bioavailability, is often administered with a bioavailability enhancing agent, piperine, which may increase the likelihood of curcumin to cause drug-herb interactions. Therefore, we also propose to test the effect of piperine and a combination of curcumin-piperine on midazolam and acetaminophen metabolism in vitro. Furthermore, we will verify our in vitro results with an in vivo clinical study examining the effects of a curcumin-piperine combination on the pharmacokinetics of a single dose of acetaminophen or midazolam in a randomized 4-way crossover study in healthy volunteers. The results from this study will provide important information on the potential of curcumin-piperine to inhibit the metabolism of co-administered drugs and cause drug-herb interactions. Ultimately, this information can be used by physicians to help guard patients from potentially unsafe combinations of herbal and traditional medicines.

描述（由申请人提供）：随着人们认识到这些天然药物的益处，补充和替代药物的使用在过去十年中急剧增加。尽管草药通常被认为是传统药物的更安全替代品，但医生越来越担心这些药物之间的相互作用。引起这种担忧的原因之一是，与传统药物不同，FDA 在向消费者出售草药补充剂之前不需要提供安全性和药物相互作用数据。通常，这种相互作用只有在严重且有时危及生命的事件发生后才会被发现。姜黄素是一种最近引起临床关注的草药补充剂，目前正处于治疗多种晚期癌症和阿尔茨海默病的临床试验中。然而，由于姜黄素对主要药物代谢酶的抑制作用，因此检查姜黄素药物与草药相互作用的潜力的数据有限。在姜黄素更广泛的治疗应用之前，应该研究姜黄素在这些药物与草药相互作用中的潜力。在这里，我们建议测试姜黄素对咪达唑仑和对乙酰氨基酚体外代谢的影响，咪达唑仑和对乙酰氨基酚分别是 I 期（细胞色素 P450 亚型 CYP3A）和 II 期（UDP-葡萄糖醛酸基转移酶和磺基转移酶）药物代谢的指标底物。姜黄素由于其生物利用度有限，通常与生物利用度增强剂胡椒碱一起服用，这可能会增加姜黄素引起药物与草药相互作用的可能性。因此，我们还建议在体外测试胡椒碱和姜黄素-胡椒碱组合对咪达唑仑和对乙酰氨基酚代谢的影响。此外，我们将通过体内临床研究验证我们的体外结果，在健康志愿者中进行随机四向交叉研究，检查姜黄素-胡椒碱组合对单剂量对乙酰氨基酚或咪达唑仑药代动力学的影响。这项研究的结果将为姜黄素-胡椒碱抑制共同给药药物的代谢并引起药物与草药相互作用的潜力提供重要信息。最终，医生可以利用这些信息来帮助患者避免潜在不安全的草药和传统药物组合。