Howrie D L, Pieniaszek H J, Fogoros R N, Juhl R P, Schary W L, Whitney C C, Dittert L W
School of Pharmacy, University of Pittsburgh, PA.
Eur J Clin Pharmacol. 1987;32(6):607-10. doi: 10.1007/BF02455996.
Moracizine (ethmozine) is a phenothiazine derivative with demonstrated antiarrhythmic activity. To characterize the pharmacokinetics and material balance relationships in humans, we have given 14C-moracizine X HCl as a single oral dose of 500 mg (50 microCi) to six healthy men. Plasma, urine, and faecal samples were collected for 7 days after administration and the concentrations of total radioactivity and intact moracizine were determined by liquid scintillation counting and HPLC, respectively. Urine and faecal recovery accounted for 95% of the administered radioactivity. Most of this radioactivity was found in the faeces (59%). Only 0.05% of the dose was recovered from urine as intact moracizine. The Cmax and AUC for moracizine equivalents of total radioactivity were 4- and 18-fold higher, respectively, than the corresponding values for intact moracizine. Additionally, both the disappearance of total radioactivity from plasma and its excretion rate into urine were slower in comparison to intact drug. Terminal t1/2 values calculated from plasma concentration-time data were 85.2 and 3.5 h for total radioactivity and intact moracizine, respectively. However, based on urinary excretion rates, the t1/2 for total radioactivity was shorter (29.3 h) while the t1/2 for intact drug was comparable (2.7 h) to the results obtained from the plasma data. The oral plasma clearance of moracizine was relatively large (2.2 l X min-1), suggesting first-pass metabolism. The estimated oral systemic availability of moracizine was 34%.
莫雷西嗪（乙吗噻嗪）是一种已证实具有抗心律失常活性的吩噻嗪衍生物。为了描述其在人体内的药代动力学和物质平衡关系，我们给6名健康男性单次口服500 mg（50 μCi）的14C - 莫雷西嗪盐酸盐。给药后7天收集血浆、尿液和粪便样本，分别通过液体闪烁计数法和高效液相色谱法测定总放射性和完整莫雷西嗪的浓度。尿液和粪便回收量占给药放射性的95%。大部分放射性存在于粪便中（59%）。仅0.05%的剂量以完整莫雷西嗪的形式从尿液中回收。总放射性的莫雷西嗪等效物的Cmax和AUC分别比完整莫雷西嗪的相应值高4倍和18倍。此外，与完整药物相比，血浆中总放射性的消失及其向尿液中的排泄速率均较慢。根据血浆浓度 - 时间数据计算的总放射性和完整莫雷西嗪的终末t1/2值分别为85.2小时和3.5小时。然而，基于尿排泄率，总放射性的t1/2较短（29.3小时），而完整药物的t1/2与从血浆数据获得的结果相当（2.7小时）。莫雷西嗪的口服血浆清除率相对较大（2.2 l·min-1），提示存在首过代谢。莫雷西嗪的估计口服全身利用率为34%。
