葡萄柚汁会改变特非那定的药代动力学，导致心电图上复极化时间延长。

Grapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram.

作者信息

Benton R E, Honig P K, Zamani K, Cantilena L R, Woosley R L

机构信息

Department of Internal Medicine, Georgetown University Medical Center, Washington, DC, USA.

出版信息

Clin Pharmacol Ther. 1996 Apr;59(4):383-8. doi: 10.1016/S0009-9236(96)90105-8.

DOI:10.1016/S0009-9236(96)90105-8

PMID:8612381

Abstract

OBJECTIVES

To establish whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by concomitant administration of grapefruit juice and to determine whether any effect of grapefruit juice is dependent on the timing of administration in relation to the dose of terfenadine.

METHODS

Twelve healthy volunteers were studied in a prospective randomized trial. The primary end points were QT prolongation on the surface electrocardiogram and the pharmacokinetic parameters: area under the concentration-time curve (AUC), maximum concentration, and time to maximum concentration of terfenadine and its acid metabolite terfenadine carboxylate. All subjects received 60 mg terfenadine twice a day with 240 ml water for 7 days. They were then randomized to drink 240 ml of double-strength grapefruit juice simultaneously with terfenadine (simultaneous group) for an additional 7 days or to drink the same dose of grapefruit juice 2 hours after terfenadine for 7 days (delayed group). Twelve timed electrocardiograms and plasma terfenadine and metabolite levels were measured on days 7 and 14.

RESULTS

None of the 12 subjects had quantifiable levels of terfenadine when the drug was administered with water. All six subjects who took terfenadine and drank grapefruit juice simultaneously had quantifiable terfenadine levels. Only two of six who drank grapefruit juice 2 hours after terfenadine had quantifiable levels. The AUC of the acid metabolite increased 55% (p < 0.05) in the simultaneous group and 22% (p = NS) in the delayed group. The mean QT interval increased from 420 to 434 msec (p < 0.05) in the simultaneous group and decreased from 408 to 407 msec (p = NS) in the delayed group.

CONCLUSIONS

Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in systemic terfenadine bioavailability and result in increases in QT interval. The clinical significance of an increase in QT interval of this magnitude is unclear.

摘要

目的

确定同时服用葡萄柚汁是否会影响特非那定的药代动力学和心电图药效学，并确定葡萄柚汁的任何作用是否取决于给药时间与特非那定剂量的关系。

方法

在一项前瞻性随机试验中对12名健康志愿者进行了研究。主要终点是体表心电图上的QT间期延长以及药代动力学参数：特非那定及其酸性代谢产物特非那定羧酸盐的浓度-时间曲线下面积（AUC）、最大浓度和达最大浓度时间。所有受试者每天两次服用60毫克特非那定，并用240毫升水冲服，共7天。然后将他们随机分为两组，一组在服用特非那定的同时饮用240毫升双倍浓度葡萄柚汁（同时服用组），持续7天；另一组在服用特非那定2小时后饮用相同剂量的葡萄柚汁，持续7天（延迟服用组）。在第7天和第14天测量12次定时心电图以及血浆特非那定和代谢产物水平。

结果

当特非那定与水一起服用时，12名受试者中没有一人的特非那定水平可量化。同时服用特非那定和饮用葡萄柚汁的6名受试者中，所有受试者的特非那定水平均可量化。在服用特非那定2小时后饮用葡萄柚汁的6名受试者中，只有2人的水平可量化。酸性代谢产物的AUC在同时服用组增加了55%（p<0.05），在延迟服用组增加了22%（p=无显著性差异）。同时服用组的平均QT间期从420毫秒增加到434毫秒（p<005），延迟服用组从408毫秒减少到407毫秒（p=无显著性差异）。