Qian M X, Liu Y H, Quan Y Z, Qiu Z Y
Zhongguo Yao Li Xue Bao. 1989 Jan;10(1):92-6.
Praziquantel (PQT) is a racemic mixture. Intragastric gavage of (-)-, (+)- and (+/-)-PQT 100 mg/kg were used to study the liver first pass effects in rabbits. HPLC was used to determine the concentration of each compound in the portal and systemic circulation, and in the bile within 4h. The results showed that all drugs were absorbed rapidly from the gut into the portal vein. The serum concentration in the portal vein were similar. However, over 90% of PQT and its enantiomers were extracted in the first passage through the liver. Intrinsic metabolic clearances of the liver of (-)-, (+)- and (+/-)-PQT were 50.3, 174.4 and 52.6 L/h, respectively. The serum concentrations of the three drugs markedly decreased in the systemic circulation, especially that of (+)-PQT. The AUC of (+)-PQT was apparently lower than that of (-)- or (+/-)-PQT. From these results, it is assumed that the first pass effects of PQT and its enantiomers in the liver are pronounced and most likely stereoselective. Also, unchanged PQT and its enantiomers were found in the bile of the rabbits.
吡喹酮（PQT）是一种外消旋混合物。通过对家兔进行胃内灌胃给予100mg/kg的（-）-、（+）-和（±）-PQT，以研究肝脏首过效应。采用高效液相色谱法（HPLC）测定4小时内门静脉、体循环及胆汁中各化合物的浓度。结果表明，所有药物均迅速从肠道吸收进入门静脉。门静脉中的血清浓度相似。然而，超过90%的PQT及其对映体在首次通过肝脏时被提取。（-）-、（+）-和（±）-PQT肝脏的内在代谢清除率分别为50.3、174.4和52.6L/h。三种药物在体循环中的血清浓度显著降低，尤其是（+）-PQT。（+）-PQT的曲线下面积（AUC）明显低于（-）-或（±）-PQT。从这些结果推测，PQT及其对映体在肝脏中的首过效应显著且很可能具有立体选择性。此外，在家兔胆汁中发现了未变化的PQT及其对映体。
