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

描述（由申请人提供）：在过去的十年中，随着这些天然药物的益处的实现，补充和替代药物的使用急剧增加。虽然草药通常被认为是传统药物的安全替代品，但医生越来越关注这些药物之间的相互作用。这种担忧的一个原因是，与传统药物不同，FDA在向消费者销售草药补充剂之前不要求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发生严重的，有时甚至危及生命的事件后才被发现。姜黄素，一种最近引起临床兴趣的草药补充剂，正在进行临床试验，用于治疗几种晚期癌症和阿尔茨海默病。然而，有限的数据已经产生检查姜黄素的药物-草药相互作用的潜力，由于抑制主要的药物代谢酶。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-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的体外代谢的影响，分别为I相（细胞色素P450亚型CYP 3A）和II相（UDP-葡萄糖醛酸转移酶和磺基转移酶）药物代谢的指标底物。姜黄素，由于其有限的生物利用度，通常与生物利用度增强剂胡椒碱一起施用，这可能增加姜黄素引起药物-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，我们将通过一项体内临床研究来验证我们的体外结果，该研究在健康志愿者中进行随机4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。这项研究的结果将提供姜黄素-胡椒碱抑制联合给药药物代谢和引起药物-草药相互作用的潜力的重要信息。最终，医生可以使用这些信息来帮助保护患者免受草药和传统药物的潜在不安全组合。

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.