The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice
The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice
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DOI：
10.1007/s002280050296
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发表时间：
1997-06-01
影响因子：
2.9
通讯作者：
Davies, DS
中科院分区：
文献类型：
--
作者：
Clifford, CP;Adams, DA;Davies, DS
目的：探讨与柚子汁合用是否对特非那丁的药代动力学和心电图药效学产生影响。方法：招募6名健康志愿者进行平衡交叉研究。每位志愿者在饮用 300 毫升水或鲜榨葡萄柚汁 30 分钟后服用 120 毫克特非那丁。两周后的第二个研究日进行了替代治疗。测量特非那定血浆浓度-时间曲线下面积（AUG）、最大特非那定浓度（C-max）和达到最大浓度的时间（t（max）），并根据表面心电图测量校正的QT（QTc）间期。结果：在两个研究日，给药后长达 24 小时内，所有 6 名受试者血浆中的特非那定均可定量。同时服用葡萄柚后，特非那定的 AUC 显着增加（中位值 40.6 vs 16.3 ng.ml(-1).h），C-max 也显着增加（中位值 7.2 vs 2.1 ng.ml(-1)）。尽管特非那定水平增加，但 t(max) 并未显着增加，中位 QTc 间期也没有显着变化。 C-max QTc 间期变化差异的 95% 置信区间为 -13 至 +38 ms。结论：柚子汁与特非那定同时服用可能会导致特非那定生物利用度增加，但本研究中观察到的增加不会导致正常受试者出现明显的心脏毒性。然而，这并不排除高危受试者在较长时间内服用更大剂量的柚子汁时出现心脏毒性的风险。
Objective: To determine whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by the concomitant administration of grapefruit juice.Methods: Six healthy volunteers were recruited for a balanced cross-over study. Each volunteer received 120 mg terfenadine 30 min after drinking 300 ml of either water or freshly squeezed grapefruit juice. The alternative treatment was administered on the second study day 2 weeks later. Measurements of the area under the terfenadine plasma concentration-time curve (AUG), maximum terfenadine concentration (C-max) and the time to maximum concentration (t(max)) were made, and the corrected QT (QTc) interval was measured from the surface electrocardiogram. Results: Terfenadine was quantifiable in plasma in all 6 subjects on both study days for up to 24 h post-dosing. The AUC of terfenadine was significantly increased by concomitant grapefruit administration (median values 40.6 vs 16.3 ng.ml(-1).h), as was the C-max (median values 7.2 vs 2.1 ng.ml(-1)). The t(max) was not significantly increased and there was no significant change in the median QTc interval despite the increased terfenadine levels. The 95% confidence interval for the difference in the change in QTc interval at C-max was -13 to +38 ms.Conclusion: Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in terfenadine bioavailability, but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects. However, this does not exclude the risk of cardiotoxicity in high-risk subjects given greater doses of grapefruit juice over longer periods of time.