Investigation of Praziquantel metabolism in isolated rat hepatocytes

Add time:08/06/2019    Source:sciencedirect.com

Isolated rat hepatocytes were used to elucidate the metabolism of praziquantel (PZQ). Our studies were designed to investigate mainly qualitative differences in the biotransformation of PZQ enantiomers. Additionally, the main metabolites cis- and trans-4-hydroxypraziquantel were determined semiquantitatively. For this purpose, racemic PZQ and both enantiomers were incubated with isolated rat hepatocytes. The incubation mixtures were investigated using high-performance liquid chromatography/mass spectrometry. Hepatocytes prepared from male Wistar rats were incubated in Krebs–Ringer buffer at 37°C for 4 h. Aliquots were withdrawn hourly throughout 4 h of incubation. We found that hepatocytes converted both enantiomers of PZQ to the major metabolites cis- and trans-4-hydroxypraziquantel. Additional metabolites were detected after incubating the S-(+)-enantiomer. These minor metabolites were identified by means of their mass/charge ratio as monohydroxypraziquantel metabolites of different, unknown structure.

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