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

Eur J Drug Metab Pharmacokinet. 1993 Jul-Sep;18(3):261-4. doi: 10.1007/BF03188806.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / drug effects
  • Drug Interactions
  • Enzyme Induction
  • Male
  • Methylcholanthrene / administration & dosage
  • Methylcholanthrene / pharmacology*
  • Phenobarbital / administration & dosage
  • Phenobarbital / pharmacology*
  • Praziquantel / pharmacokinetics*
  • Premedication
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Methylcholanthrene
  • Praziquantel
  • Cytochrome P-450 Enzyme System
  • Phenobarbital