EFFECTS OF PHENOBARBITAL AND 3-METHYLCHOLANTHRENE PRETREATMENT ON THEPHARMACOKINETICS OF PRAZIQUANTEL IN RATS

The effects of phenobarbital (PB) and 3-methylcholanthrene (MC) pretre atment on the pharmacokinetics of praziquantel (PZQ), a schistosomicid e were studied in Sprague-Dawley rats. Blood samples at different time intervals were obtained by severing the tail vein and were analyzed f or unchanged PZQ by HPLC. The PB-pretreated rats showed a 6-fold decre ase in AUC, a 5-fold decrease in C-max and an 8-fold increase in CL(to t) compared to the saline treated controls. The MC-pretreated rats and their olive-oil treated controls did not show any statistically signi ficant differences in the above parameters. These results suggest that PZQ is extensively metabolised by PB-inducible cytochrome P-450 isofo rms 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.