RED WINE EFFECTS ON CYTOCHROME P450 3A4 ACTIVITY IN HEALTHY INDIVIDUALS

红酒对健康个体细胞色素 P450 3A4 活性的影响

• 批准号: 6304507
• 负责人: SHIRLEY TSUNODA
• 金额: $ 4.27万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6304507
• 关键词: alcoholic beverages; biomarker; blood chemistry; clinical research; clinical trial phase I; cyclosporines; cytochrome P450; drug metabolism; drug screening /evaluation; enzyme activity; enzyme inhibitors; fluorescence polarization; human subject; immunologic assay /test; oxygenases; pharmacokinetics

Commonly ingested compounds such as grapefruit juice and red wine may have effects on the therapeutic efficacy of drugs metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. Our previous in vitro work suggests that red wine may inhibit CYP3A4 to a similar degree as found with grapefruit juice. Our current investigation purposes to determine whether inhibition of CYP3A4 by red wine can result in clinically significant elevations in drug levels. This study will investigate twelve healthy volunteers in a two-way cross-over study. A single 8 mg/kg oral dose of cyclosporine (a marker for CYP3A4 activity) will be given with water and red wine on separate occasions. Whole blood levels will be drawn and analyzed by a specific fluorescence polarization immunoassay, and the pharmacokinetics of cyclosporine will be compared.

通常摄入的化合物，如葡萄柚汁和红葡萄酒，可能会对细胞色素P450 3A 4（CYP 3A 4）酶代谢的药物的疗效产生影响。 我们之前的体外研究表明，红葡萄酒可能会抑制CYP 3A 4，其抑制程度与葡萄柚汁相似。 我们目前的研究目的是确定红葡萄酒对CYP 3A 4的抑制是否会导致药物水平的临床显著升高。 本研究将在双向交叉研究中对12名健康志愿者进行研究。 单次口服8 mg/kg环孢素（CYP 3A 4活性的标志物），在不同的情况下用水和红葡萄酒给药。 将抽取全血水平并通过特异性荧光偏振免疫测定法进行分析，并将比较环孢素的药代动力学。