Benedek I H, King S Y, Powell R J, Agra A M, Schary W L, Pieniaszek H J
Du Pont Merck Pharmaceutical Company, Newark, Delaware 19714.
J Clin Pharmacol. 1992 Jun;32(6):558-63. doi: 10.1177/009127009203200612.
Moricizine HCl, a new orally active antiarrhythmic agent, induces its own hepatic metabolism and consequently may interfere with the metabolism of warfarin, a drug used commonly by cardiac patients that also is subject to extensive hepatic metabolism. Both drugs are also highly protein bound in plasma. To assess the possibility of an interaction, single-dose sodium warfarin (25 mg oral Coumadin, Du Pont Pharmaceuticals, Wilmington, DE) pharmacokinetics, pharmacodynamics; and plasma protein binding were examined in 12 healthy male volunteers 14 days before and 14 days after starting chronic oral moricizine HCl administration (250 mg every 8 hours). The terminal elimination rate constant of warfarin was increased by about 10% when measured in the presence of chronic moricizine administration. However, oral plasma clearance, apparent volume of distribution, maximum peak plasma concentration, time to reach peak concentration, and protein binding were unaffected. More importantly, there was no evidence of a pharmacodynamic interaction based on the prothrombin time profile. It was concluded that no clinically significant interaction occurs under these conditions.
盐酸莫雷西嗪是一种新型口服活性抗心律失常药物，可诱导自身肝脏代谢，因此可能干扰华法林的代谢。华法林是心脏病患者常用的药物，也会经历广泛的肝脏代谢。这两种药物在血浆中也都与蛋白质高度结合。为评估相互作用的可能性，在12名健康男性志愿者中，于开始长期口服盐酸莫雷西嗪（每8小时250毫克）给药前14天和给药后14天，检测了单剂量华法林钠（25毫克口服香豆素，杜邦制药公司，特拉华州威尔明顿）的药代动力学、药效学以及血浆蛋白结合情况。在长期服用莫雷西嗪的情况下进行测量时，华法林的终末消除速率常数增加了约10%。然而，口服血浆清除率、表观分布容积、最大血浆峰浓度、达到峰浓度的时间以及蛋白结合均未受影响。更重要的是，基于凝血酶原时间曲线，没有药效学相互作用的证据。得出的结论是，在这些条件下不会发生具有临床意义的相互作用。
