Honig P K, Woosley R L, Zamani K, Conner D P, Cantilena L R
Division of Clinical Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Clin Pharmacol Ther. 1992 Sep;52(3):231-8. doi: 10.1038/clpt.1992.135.
Terfenadine is a nonsedating H1-antagonist that when overdosed, used with hepatic compromise, or when given with ketoconazole results in accumulation of parent terfenadine, prolongation of the QT interval, and torsades de pointes in susceptible patients. Nine subjects were given the recommended dose of terfenadine (60 mg every 12 hours) for 7 days before initiation of oral erythromycin (500 mg every 8 hours). All subjects increased metabolite concentrations after the addition of erythromycin for 1 week. The maximum concentration of metabolite increased by a mean of 107% and the mean metabolite area under the concentration-time curve increased by 170%. Three subjects accumulated unmetabolized terfenadine after administration of erythromycin for 1 week. Electrocardiographic data revealed changes in QT intervals and ST-U complexes in a subset of subjects who accumulated terfenadine. We conclude that erythromycin alters the metabolism of terfenadine, leading to accumulation of terfenadine in certain individuals that is associated with altered cardiac repolarization.
特非那定是一种非镇静性H1拮抗剂，过量服用、与肝功能损害同时使用或与酮康唑合用时，会导致母体特非那定蓄积，QT间期延长，并使易感患者发生尖端扭转型室速。9名受试者在开始口服红霉素（每8小时500mg）前，按推荐剂量服用特非那定（每12小时60mg）7天。在加用红霉素1周后，所有受试者的代谢物浓度均升高。代谢物的最大浓度平均升高了107%，浓度-时间曲线下的平均代谢物面积增加了170%。3名受试者在服用红霉素1周后出现未代谢特非那定的蓄积。心电图数据显示，在蓄积特非那定的部分受试者中，QT间期和ST-U复合波有变化。我们得出结论，红霉素会改变特非那定的代谢，导致特非那定在某些个体中蓄积，这与心脏复极改变有关。
