The liver first pass effects and bile concentrations of (-)-, (+)- and (+/-)-praziquantel in rabbits

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.