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: 7469535
• 负责人: Laurie Pauline Volak
• 金额: $ 2.75万
• 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 2008-08-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7469535
• 关键词: Acetaminophen; Acids; Adenocarcinoma Cell; Advanced Malignant Neoplasm; Alzheimer' s Disease; Ascorbic Acid; Bacterial Infections; Bilirubin; Biological Availability; Biological Models; Bispecific Antibody 2B1; Black Pepper; Blood; Blood specimen; COS-1 Cells; CYP1A1 gene; CYP2E1 gene; CYP3A4 gene; Capsaicin; Carotene; Cell Line; Cells; Class; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Colon Adenocarcinoma; Complementary and alternative medicine; Controlled Study; Cross-Over Studies; Curcumin; Cystic Fibrosis; Cytochrome P450; D-617; Data; Disease; Dose; Drug Interactions; Drug Kinetics; Enzymes; Event; Glucuronosyltransferase; Herb-Drug Interactions; Herbal Medicine; Human; In Vitro; Intestines; Kidney; Knowledge; Laboratory Finding; Lead; Life; Liver; Liver Extract; Liver Microsomes; Malaria; Malignant Neoplasms; Mediating; Metabolism; Midazolam; Monitor; Monkeys; Mus; Mycophenolic Acid; Nitrophenol; Nutritional; Patients; Penetration; Pharmaceutical Preparations; Pharmacodynamics; Phase; Physicians; Powder dose form; Protein Isoforms; Psychomotor Performance; Publishing; Randomized; Rattus; Safety; Sales; Sampling; Selenium; Testing; Therapeutic; Therapeutic Effect; Traditional Medicine; Triazolam; Tumeric; United States Food and Drug Administration; Urine; Verapamil; base; cytochrome P450 3A; drug metabolism; gallocatechol; healthy volunteer; in vitro Model; in vivo; indexing; interest; norverapamil; oxidation; piperine; sulfation; sulfotransferase

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）：在过去的十年中，随着这些天然药物的好处被认识到，补充和替代药物的使用急剧增加。虽然草药通常被认为是一种比传统药物更安全的替代品，但医生们越来越担心这些药物之间的相互作用。引起这种担忧的一个原因是，与传统药物不同，在向消费者出售草药补充剂之前，FDA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严重的、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兴趣的草药补充剂，目前正在进行临床试验，用于治疗几种晚期癌症和阿尔茨海默病。然而，由于姜黄素对主要药物代谢酶的抑制作用，研究姜黄素在药物-草药相互作用中的潜力的数据有限。在姜黄素更广泛的治疗应用之前，姜黄素对这些药物-草药相互作用的潜力应该进行研究。本研究拟检测姜黄素对咪达唑胺和对乙酰氨基酚体外代谢的影响，分别为I期（细胞色素P450异构体CYP3A）和II期（葡萄糖醛基转移酶和硫代转移酶）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，这可能会增加姜黄素引起药物-草药相互作用的可能性。因此，我们也拟在体外测试胡椒碱和姜黄素-胡椒碱联合使用对咪达唑仑和对乙酰氨基酚代谢的影响。此外，我们将在健康志愿者中进行一项随机4向交叉研究，验证姜黄素-胡椒碱组合对单剂量对乙酰氨基酚或咪达唑仑的药代动力学影响的体内临床研究。本研究的结果将为姜黄素-胡椒碱抑制共给药药物代谢和引起药物-草药相互作用的潜力提供重要信息。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可能不安全的组合。