Honig P K, Worham D C, Zamani K, Mullin J C, Conner D P, Cantilena L R
Division of Clinical Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Clin Pharmacol Ther. 1993 Jun;53(6):630-6. doi: 10.1038/clpt.1993.83.
Terfenadine is rapidly and nearly completely biotransformed during a first pass to an active acid metabolite. Accumulation of unmetabolized terfenadine has been associated with altered cardiac repolarization. Drug-drug interactions resulting in the accumulation of terfenadine have been reported for ketoconazole and erythromycin. Six subjects were given the recommended dose of terfenadine (60 mg every 12 hours) for 7 days before initiation of oral fluconazole (200 mg once daily). The mean metabolite area under the concentration-time curve increased by 34% and the time to maximum concentration of the metabolite was delayed from 2.3 to 4 hours by concurrent fluconazole. Unmetabolized terfenadine was not present in any subject, and cardiac repolarization was not significantly changed from baseline during any phase of the study. We conclude that a pharmacokinetic interaction between terfenadine and fluconazole exists; however, the absence of accumulation of parent terfenadine in plasma suggests that a clinically significant interaction is unlikely.
特非那定在首过效应期间迅速且几乎完全生物转化为一种活性酸代谢物。未代谢的特非那定蓄积与心脏复极化改变有关。已报道酮康唑和红霉素会导致药物相互作用，致使特非那定蓄积。6名受试者在开始口服氟康唑（每日一次，200毫克）之前，按推荐剂量服用特非那定（每12小时60毫克），共7天。同时服用氟康唑时，代谢物浓度 - 时间曲线下的平均面积增加了34%，代谢物达到最大浓度的时间从2.3小时延迟至4小时。任何受试者体内均未出现未代谢的特非那定，且在研究的任何阶段，心脏复极化与基线相比均无显著变化。我们得出结论，特非那定与氟康唑之间存在药代动力学相互作用；然而，血浆中母体特非那定未蓄积表明不太可能存在具有临床意义的相互作用。
