Authors : Sanaa Botros , Sayed Seif el-Din , Naglaa El-Lakkany , Abdel Nasser Sabra and Fatma Ebeid
Abstract: The level of drug metabolizing enzymes (CYP450 and cyt b5) and the bioavailability of praziquantel (PZQ) were investigated in batches of mice infected with Schistosoma mansoni (S. mansoni) displaying either a decreased susceptibility to PZQ (EE2 and BANL-isolates), or a normal susceptibility to the drug (CD isolate). Each batch was divided into two groups. The first one comprising 50 animals was further subdivided into 5 subgroups. Subgroups 1 to 4 were treated with oral PZQ at 25, 50, 100 and 200 mg kg 1 for 5 consecutive days beginning on the 7th week after infection, while the fifth subgroup was administered the vehicle only as a control. Animals were perfused 9 weeks post infection, and worms were counted to estimate PZQ ED50. CYP450 and cyt b5 were examined in hepatic microsomes of infected untreated mice and of infected mice treated with 25 mg kg 1 and 200 mg kg 1 PZQ. The second group comprising 77 animals was given PZQ 7 weeks post infection and was further subdivided into 11 subgroups, sacrificed at 2, 5, 15, 30, 60, 90, 120,150, 180, 240 and 360 minutes post dosing to study pharmacokinetic parameters of PZQ. Mice harboring S. mansoni isolates having higher PZQ ED50 (170.3 mg kg 1 for EE2 and 249.9 mg kg 1 for BANL vs 82.96 mg kg 1 for CD) had higher levels of CYP450 and cyt b5, a PZQ Cmax decreased by 19-30% and AUC0-6hr decreased by 57-74%. Data may suggest that S. mansoni isolates that are less sensitive to PZQ induce a lower inhibition of hepatic drug metabolizing enzymes, with a consequently higher metabolic transformation of PZQ.
Sanaa Botros , Sayed Seif el-Din , Naglaa El-Lakkany , Abdel Nasser Sabra and Fatma Ebeid , 2006. Drug Metabolizing Enzymes and Praziquantel Bioavailability in Mice Harboring Schistosoma mansoni Isolates of Different Drug Susceptibilities. International Journal of Tropical Medicine, 1: 11-17.