Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics of praziquantel in rats.

The effects of phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment on the pharmacokinetics of praziquantel (PZQ), a schistosomicide were studied in Sprague-Dawley rats. Blood samples at different time intervals were obtained by severing the tail vein and were analyzed for unchanged PZQ by HPLC. The PB-pretreated rats showed a 6-fold decrease in AUC, a 5-fold decrease in Cmax and an 8-fold increase in CLtot compared to the saline treated controls. The MC-pretreated rats and their olive-oil treated controls did not show any statistically significant differences in the above parameters. These results suggest that PZQ is extensively metabolised by PB-inducible cytochrome P-450 isoforms and not by MC-inducible isoforms. These findings also suggest that the bioavailability of praziquantel could be altered to a significant extent in humans taking drugs that are phenobarbital type inducers.