Siddoway L A, Schwartz S L, Barbey J T, Woosley R L
Department of Medicine, Georgetown University of School of Medicine, Washington, D.C.
Am J Cardiol. 1990 Feb 20;65(8):21D-25D; discussion 68D-71D. doi: 10.1016/0002-9149(90)91413-z.
Moricizine is well absorbed after oral administration and undergoes extensive first-pass metabolism. The drug has a large apparent volume of distribution (approximately 4 liters/kg), exhibits extensive plasma protein binding (approximately 95%) and produces at least 30 metabolites. Indirect evidence indicates that some of those metabolites may be pharmacologically active. The elimination half-life of moricizine is 2 to 6 hours, but its duration of antiarrhythmic action is much longer suggesting active metabolites. Moricizine induces its own metabolism with no change in pharmacologic effect. It also induces the metabolism of theophylline and specific pathways of antipyrine. Cimetidine reduces metabolism of moricizine but does not alter its pharmacologic effects. This observation provides further support for the hypothesis that the metabolites of moricizine contribute to the pharmacologic actions during therapy and indicate that plasma level monitoring is not likely to be of value. There are no known clinically significant pharmacokinetic interactions between moricizine and digoxin, warfarin or propranolol. Excessive prolongation of the PR interval has been seen in some patients receiving both digoxin and moricizine, probably due to additive electrophysiologic effects of the 2 drugs.
莫雷西嗪口服后吸收良好，且经历广泛的首过代谢。该药具有较大的表观分布容积（约4升/千克），表现出广泛的血浆蛋白结合（约95%），并产生至少30种代谢产物。间接证据表明，其中一些代谢产物可能具有药理活性。莫雷西嗪的消除半衰期为2至6小时，但其抗心律失常作用的持续时间长得多，提示存在活性代谢产物。莫雷西嗪可诱导自身代谢，而药理作用无变化。它还可诱导茶碱的代谢以及安替比林的特定代谢途径。西咪替丁可降低莫雷西嗪的代谢，但不改变其药理作用。这一观察结果为以下假说提供了进一步支持，即莫雷西嗪的代谢产物在治疗期间有助于药理作用，并表明血浆水平监测可能无价值。莫雷西嗪与地高辛、华法林或普萘洛尔之间不存在已知的具有临床意义的药代动力学相互作用。在一些同时接受地高辛和莫雷西嗪治疗的患者中，曾观察到PR间期过度延长，这可能是由于这两种药物的相加电生理效应所致。
