title: Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics of praziquantel in rats.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Zimbabwe, Harare.
authors.forename: C M
authors.initials: CM
authors.lastname: Masimirembwa
authors.forename: Y S
authors.initials: YS
authors.lastname: Naik
authors.forename: J A
authors.initials: JA
authors.lastname: Hasler
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004347:Drug Interactions; D004790:Enzyme Induction; D008297:Male; D008748:Methylcholanthrene / Q000008:administration & dosage / Q000494:pharmacology*; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D011223:Praziquantel / Q000493:pharmacokinetics*; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008748:Methylcholanthrene; D011223:Praziquantel; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital