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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Atorvastatin does not produce a clinically significant effect on the pharmacokinetics of terfenadine.
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Atorvastatin does not produce a clinically significant effect on the pharmacokinetics of terfenadine.

机译：阿托伐他汀对特非那定的药代动力学没有产生临床上显着的影响。

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摘要

The effect of atorvastatin, a CYP3A4 substrate, on the pharmacokinetics of terfenadine and its carboxylic acid metabolite, fexofenadine, were evaluated. Single 120-mg doses of terfenadine were given 2 weeks apart to healthy volunteers with 80-mg daily doses of atorvastatin administered from 7 days before through 2 days after the second terfenadine dose. Concentrations of terfenadine and fexofenadine were measured for 72 hours after each terfenadine dose. Administration of terfenadine alone or in combination with atorvastatin produced no alterations in the QTc interval. For terfenadine, atorvastatin coadministration produced an 8% decrease in maximum concentration (Cmax), a 35% increase in area under the concentration-time curve extrapolated to infinity (AUC0-infinity), and a 2% decrease in elimination half-life (t1/2). For fexofenadine, atorvastatin coadministration produced a 16% decrease in Cmax, a 2% decrease in AUC0-infinity and a 51 % increase in t1/2. None of these changes achieved statistical significance. Coadministration of atorvastatin with terfenadine does not result in a clinically significant drug interaction. Because 80 mg is the highest atorvastatin dose used clinically, drug interactions mediated by CYP3A4 inhibition are unlikely in clinical practice.
机译：评估了CYP3A4底物阿托伐他汀对特非那定及其羧酸代谢产物非索非那定的药代动力学的影响。从健康的志愿者开始，每隔2周就给120毫克特非那定单剂量服用，从第二次芬非那定前7天到第二天2天后，每天服用80毫克阿托伐他汀。每次服用芬非那定后72小时，测量芬非那定和非索非那定的浓度。单独使用特非那定或与阿托伐他汀合用不会导致QTc间隔改变。对于特非那定，阿托伐他汀共同给药可使最大浓度（Cmax）降低8％，在浓度-时间曲线下外推至无穷大（AUC0-无穷大），面积增加35％，消除半衰期（t1）减少2％ / 2）。对于非索非那定，阿托伐他汀共同给药可使Cmax降低16％，AUC0-infinity降低2％，t1 / 2升高51％。这些变化均未达到统计学意义。阿托伐他汀与特非那定的共同给药不会导致临床上显着的药物相互作用。由于80 mg是临床上使用的最高阿托伐他汀剂量，因此在临床实践中不太可能通过CYP3A4抑制作用介导药物相互作用。

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