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: 6264100
• 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: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264100
• 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 suggets that redwine 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.

葡萄柚汁和红酒等常见摄入的化合物可能会影响细胞色素 P450 3A4 (CYP3A4) 酶代谢的药物的治疗效果。 我们之前的体外研究表明，红酒可能会抑制 CYP3A4，其程度与葡萄柚汁的抑制程度相似。 我们目前的研究目的是确定红酒对 CYP3A4 的抑制是否会导致临床上显着的药物水平升高。本研究将通过双向交叉研究调查 12 名健康志愿者。 单次口服 8 mg/kg 环孢素（CYP3A4 活性标记物）将分别与水和红酒一起服用。 将通过特定的荧光偏振免疫测定法抽取并分析全血水平；并对环孢素的药代动力学进行比较。