红酒与西沙必利的相互作用：与葡萄柚汁的比较。

Red wine-cisapride interaction: comparison with grapefruit juice.

作者信息

Offman E M, Freeman D J, Dresser G K, Munoz C, Bend J R, Bailey D G

机构信息

Departments of Medicine and Pharmacology and Toxicology, London Health Sciences Centre and the University of Western Ontario, Canada.

出版信息

Clin Pharmacol Ther. 2001 Jul;70(1):17-23. doi: 10.1067/mcp.2001.116892.

DOI:10.1067/mcp.2001.116892

PMID:11452240

Abstract

OBJECTIVES

Our objective was to compare the interactions of red wine and grapefruit juice with cisapride.

METHODS

The oral pharmacokinetics of cisapride, its norcisapride metabolite, and electrocardiographic QTc interval were determined over a 24-hour period after administration of cisapride 10 mg with 250 mL grapefruit juice, red wine (cabernet sauvignon), or water in a randomized 3-way crossover study in 12 healthy men.

RESULTS

The cisapride area under the concentration-time curve (AUC) and the maximum plasma drug concentration after single-dose administration (C(max)) with grapefruit juice were 151% (P <.01) and 168% (P <.001), respectively, of those with water. The increase in cisapride AUC and C(max) was variable among individuals; however, cisapride AUC and C(max) were enhanced by the same proportion. The time to reach maximum concentration after drug administration (t(max)) and the apparent elimination half-life (t((1/2)) for cisapride and the pharmacokinetics of norcisapride were not altered. Norcisapride/cisapride ratios were reduced. Cisapride AUC and C(max) with red wine were 115% (difference not statistically significant) and 107% (difference not statistically significant), respectively, of those with water. The cisapride t(max) was slightly longer. Cisapride t((1/2)) and norcisapride pharmacokinetics were not different. The norcisapride/cisapride ratio at cisapride C(max) was lower. One subject had a doubling in cisapride AUC and C(max) and a decrease in norcisapride/cisapride ratios with red wine and also had the largest interaction with grapefruit juice. QTc interval was unchanged in all treatment groups and individuals.

CONCLUSIONS

A single glass of grapefruit juice produced an individual-dependent variable increase in the systemic availability of cisapride by inhibition of intestinal cytochrome P450 3A4 (CYP3A4) activity. The identical volume of red wine caused only minor changes in cisapride pharmacokinetics despite some inhibition of CYP3A4 in most individuals. However, even this amount of red wine may cause a marked interaction similar to that for grapefruit juice in individuals with a preexisting high intestinal CYP3A4 content.

摘要

目的

我们的目的是比较红酒和葡萄柚汁与西沙必利的相互作用。

方法

在一项随机三交叉研究中，对12名健康男性给予10毫克西沙必利，同时饮用250毫升葡萄柚汁、红酒（赤霞珠）或水，之后在24小时内测定西沙必利及其去甲西沙必利代谢物的口服药代动力学以及心电图QTc间期。

结果

与水相比，服用葡萄柚汁后西沙必利的浓度 - 时间曲线下面积（AUC）和单剂量给药后的最大血浆药物浓度（C(max)）分别为水的151%（P <.01）和168%（P <.001）。西沙必利AUC和C(max)的增加在个体间存在差异；然而，西沙必利AUC和C(max)以相同比例升高。给药后达到最大浓度的时间（t(max)）以及西沙必利的表观消除半衰期（t((1/2))）和去甲西沙必利的药代动力学未改变。去甲西沙必利/西沙必利比值降低。与水相比，服用红酒后西沙必利的AUC和C(max)分别为水的115%（差异无统计学意义）和107%（差异无统计学意义）。西沙必利的t(max)略长。西沙必利的t((1/2))和去甲西沙必利的药代动力学无差异。在西沙必利C(max)时去甲西沙必利/西沙必利比值较低。一名受试者服用红酒后西沙必利的AUC和C(max)加倍，去甲西沙必利/西沙必利比值降低，并且与葡萄柚汁的相互作用也最大。所有治疗组和个体的QTc间期均未改变。

结论

一杯葡萄柚汁通过抑制肠道细胞色素P450 3A4（CYP3A4）活性，使西沙必利的全身可用性产生个体依赖性的可变增加。相同体积的红酒尽管在大多数个体中对CYP3A4有一定抑制作用，但仅引起西沙必利药代动力学的轻微变化。然而，即使是这种量的红酒，对于肠道CYP3A4含量原本就高的个体，也可能引起与葡萄柚汁类似的显著相互作用。