Pohjola-Sintonen S, Viitasalo M, Toivonen L, Neuvonen P
First Department of Medicine, Helsinki University Central Hospital, Finland.
Eur J Clin Pharmacol. 1993;45(2):191-3. doi: 10.1007/BF00315505.
Terfenadine, a nonsedating H1-selective antihistamine, is widely used in many countries. We report pharmacokinetic results in a patient who developed a prolonged QT-interval in ECG and symptomatic torsades de pointes ventricular tachycardia as a consequence of the interaction of itraconazole and terfenadine. Both drugs were taken in the recommended doses: terfenadine 60 mg b.d. and itraconazole 100 mg b.d. Terfenadine metabolism was delayed by itraconazole, leading to an increased level of unmetabolised terfenadine. Seven weeks after the cessation of itraconazole treatment, terfenadine was rapidly metabolized to its active metabolite and did not prolong the QT-interval when given as a single provocation dose (120 mg). The findings suggest that intraconazole in therapeutic doses inhibits terfenadine metabolism. It is also possible that unmetabolised terfenadine alone, without an increased level of its active metabolite, may cause torsades de pointes. The concomitant use of terfenadine and itraconazole (and ketoconazole) should be avoided.
特非那定是一种非镇静性H1选择性抗组胺药，在许多国家广泛使用。我们报告了一名患者的药代动力学结果，该患者因伊曲康唑与特非那定相互作用，心电图出现QT间期延长，并出现症状性尖端扭转型室性心动过速。两种药物均按推荐剂量服用：特非那定每日两次，每次60毫克；伊曲康唑每日两次，每次100毫克。伊曲康唑使特非那定的代谢延迟，导致未代谢的特非那定水平升高。伊曲康唑治疗停止7周后，特非那定迅速代谢为其活性代谢物，单次激发剂量（120毫克）给药时未延长QT间期。这些发现表明，治疗剂量的伊曲康唑会抑制特非那定的代谢。也有可能仅未代谢的特非那定，在其活性代谢物水平未升高的情况下，就可能导致尖端扭转型室性心动过速。应避免同时使用特非那定和伊曲康唑（以及酮康唑）。
