Investigation of Praziquantel metabolism in isolated rat hepatocytes

Isolated rat hepatocytes were used to elucidate the metabolism of praziquan tel (PZQ). Our studies were designed to investigate mainly qualitative diff erences in the biotransformation of PZQ enantiomers. Additionally, the main metabolites cis- and trans-4-hydroxypraziquantel were determined serniquan titatively. For this purpose, racemic PZQ and both enantiomers were incubat ed with isolated rat hepatocytes. The incubation mixtures were investigated using high-performance liquid chromatography/mass spectrometry. Hepatocyte s prepared from male Wistar rats were incubated in Krebs-Ringer buffer at 3 7 degreesC for 4 h. Adiquots were withdrawn hourly throughout 4 h of incuba tion. We found that hepatocytes converted both enantiomers of PZQ to the ma jor metabolites cis- and trans-4-hydroxypraziquantel. Additional metabolite s were detected after incubating the S-(+)-enantiomer. These minor metaboli tes were identified by means of their mass/charge ratio as monohydroxyprazi quantel metabolites of different, unknown structure. (C) 2001 Elsevier Scie nce B.V. All rights reserved.