GARLIC METABOLISM AND CYTOCHROME P450 MODULATION

大蒜代谢和细胞色素 P450 调节

• 批准号: 7603476
• 负责人: DANNY D SHEN
• 金额: $ 1.39万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603476
• 关键词: Acute; Bupropion; CYP1A2 gene; Caffeine; Chlorzoxazone; Chronic; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Digoxin; Drug Kinetics; Drug Prescriptions; Enzymes; Funding; Garlic; Garlic Extract; Garlicin; Grant; Herb; Institution; Intestines; Measures; Metabolism; Metoprolol; Midazolam; Nature; Omeprazole; P-Glycoprotein; Pharmaceutical Preparations; Preparation; Research; Research Personnel; Resources; Safety; Source; Tablets; Tolbutamide; United States National Institutes of Health; aged; allyl sulfide; capsule; day; in vivo; treatment duration

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 人们越来越关注柜台销售的许多草药产品的质量、功效和安全性。 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。这项研究的总体目标是研究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 Aged大蒜提取物片剂对主要药物代谢细胞色素 P450 酶（CYP1A2、2B6、2E1、 2C9、2C19、2D6、3A4/5) 和健康受试者的肠道流出转运蛋白 P-糖蛋白 (Pgp)。 CYP 和 Pgp 的体内活性将使用 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“混合物”在急性（2-4 天）、慢性（28-39 天），以及停止使用每种大蒜制剂治疗后不久（10 天）。 还将研究每种大蒜补充剂的生物活性成分衍生的代谢物的药代动力学。 这些探索研究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。