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

通常摄入的化合物，如葡萄汁和红酒，可能会影响由细胞色素P450 3A4(CYP3A4)酶代谢的药物的治疗效果。我们之前的体外工作表明，红酒可能会抑制CYP3A4，其程度与葡萄柚汁相似。我们目前的研究目的是确定红酒对CYP3A4的抑制是否可以导致临床上药物水平的显著升高。这项研究将对12名健康志愿者进行双向交叉研究。单次口服8毫克/公斤的环孢素(CYP3A4活性的标志)将在不同的场合与水和红酒一起服用。将提取全血浓度，并用特异的荧光偏振免疫分析法进行分析；并将比较环孢素的药代动力学。

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.