Woosley R L, Morganroth J, Fogoros R N, McMahon F G, Humphries J O, Mason D T, Williams R L
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Am J Cardiol. 1987 Oct 16;60(11):35F-39F. doi: 10.1016/0002-9149(87)90718-1.
Moricizine HCl is a phenothiazine derivative with antiarrhythmic properties. It was developed in the USSR and is now undergoing clinical evaluation. Although preliminary work has shown moricizine HCl to be effective in treating both atrial and ventricular arrhythmias, little is known of its pharmacokinetics. There is a 4-fold variability in range for its elimination half-life and in volumes of distribution and clearance. There is a linear relation for peak plasma levels and area under the plasma concentration/time curve with regard to single-dose administration of moricizine HCl. The bioavailability of moricizine HCl connotes extensive first-pass effect, or presystemic metabolism. Very little of moricizine is excreted unchanged; it is extensively metabolized to certain compounds that are present in plasma for extended periods. Moricizine is extensively (92% to 95%) bound to plasma protein. Its coadministration with cimetidine leads to additive systemic effects; however, there is no evidence of alterations in steady-state levels when moricizine HCl is coadministered with digoxin. Because moricizine is a drug with active metabolites, its concentration/effect profile is complex; this poses a challenge for accurate dose titration. This may, however, be a helpful challenge in that the metabolites may one day prove useful in therapy. This surmise warrants further study.
盐酸莫雷西嗪是一种具有抗心律失常特性的吩噻嗪衍生物。它由苏联研发，目前正在进行临床评估。尽管初步研究表明盐酸莫雷西嗪在治疗房性和室性心律失常方面有效，但其药代动力学却鲜为人知。其消除半衰期、分布容积和清除率的范围存在4倍的变异性。单剂量给予盐酸莫雷西嗪时，血浆峰值水平与血浆浓度/时间曲线下面积呈线性关系。盐酸莫雷西嗪的生物利用度意味着广泛的首过效应或系统前代谢。莫雷西嗪极少以原形排泄；它会广泛代谢为某些在血浆中长时间存在的化合物。莫雷西嗪与血浆蛋白广泛结合（92%至95%）。它与西咪替丁合用会产生相加的全身效应；然而，当盐酸莫雷西嗪与地高辛合用时，没有证据表明稳态水平会发生改变。由于莫雷西嗪是一种具有活性代谢产物的药物，其浓度/效应曲线很复杂；这给准确的剂量滴定带来了挑战。然而，这可能是一个有益的挑战，因为这些代谢产物有朝一日可能被证明在治疗中有用。这一推测值得进一步研究。
