GARLIC METABOLISM AND CYTOCHROME P450 MODULATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 人们越来越关注许多在柜台出售的草药产品的质量、功效和安全性。 一个主要的安全问题是草药和药物之间可能发生不良相互作用。 大蒜补充剂是美国最畅销的草药产品之一。这项拟议研究的总体目标是调查三种常用大蒜补充剂的调节作用，即，Nature Way大蒜素片、KAL 1500大蒜油胶囊和Kyolic Formula 100陈年大蒜提取物片对健康受试者主要药物代谢细胞色素P450酶（CYP 1A 2、2B 6、2 E1、2C 9、2C 19、2D 6、3A 4/5）和肠道外排转运蛋白P-糖蛋白（Pgp）活性的影响。 在急性（2-4天）、慢性（28-39天）和每种大蒜制剂治疗停止后不久（10天），将使用CYP和Pgp特异性药物底物探针（咖啡因、安非他酮、氯唑沙宗、甲苯磺丁脲、奥美拉唑、美托洛尔、咪达唑仑和地高辛）的“鸡尾酒”测定CYP和Pgp的体内活性。 还将研究来自每种大蒜补充剂的生物活性成分的代谢物的药代动力学。 从这些探测研究中产生的信息将使我们能够预测大蒜补充剂和处方药之间的潜在相互作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is growing concern over the quality, efficacy and safety of the many herbal products sold over the counter. A major safety concern is the potential for adverse interactions between herbs and drugs. Garlic supplement is among the top selling herbal products in the U.S. The overall objective of this proposed research is to investigate the modulating effects of three commonly used garlic supplements, i.e., Nature Way Garlicin tablet, KAL 1500 garlic oil capsule, and Kyolic Formula 100 Aged Garlic Extract tablets, on the activity of major drug-metabolizing cytochrome P450 enzymes (CYP1A2, 2B6, 2E1, 2C9, 2C19, 2D6, 3A4/5) and the intestinal efflux transporter P-glycoprotein (Pgp) in healthy subjects. In vivo activity of CYPs and Pgp will be measured using "cocktails" of CYP- and Pgp-specific drug substrate probes (caffeine, bupropion, chlorzoxazone, tolbutamide, omeprazole, metoprolol midazolam and digoxin) following acute (2-4 days), chronic (28-39 days), and shortly after following discontinuation (10 days) of treatment with each garlic preparation. Pharmacokinetics of metabolites derived from the bioactive constituents for each of the garlic supplements will also be investigated. Information generated from these probe studies will allow us to predict potential interactions between garlic supplements and prescription drugs.