Comparative efficacy and bioavailability of different praziquantel brands.
This study investigates the efficacy, bioavailability and drug metabolizing enzymes mainly involved in the metabolism of the commercial brands of praziquantel (PZQ) in Egypt in comparison with the original pure powder. Mice infected with PZQ-susceptible (CD) or PZQ-insusceptible (EE2) Schistosoma mansoni isolates were divided each into seven groups, six of them received PZQ brands (Distocide, Epiquantel, Biltricide, Bilharzid, Praziquantel, and pure PZQ), while the seventh one was left as infected untreated. Seven weeks post-infection, worms were quantified and hepatic CYP450 and CYT b5 were examined. For PZQ pharmacokinetics, groups of normal mice were given the different PZQ brands and divided into subgroups, killed at 2, 5, 15, 30, 60, 90, 120,150, 180, 240 and 360 min post-dosing. Physicochemical examination revealed better dissolution rates for Biltricide, Distocide and PZQ T3A rather than Epiquantel and Bilharzid. Significant decrease in worm burden was recorded in all groups of mice regardless of the brand of PZQ used, but with better results obtained with CD isolate rather than the EE2 isolate. Biltricide and Distocide showed higher C(max) and AUC(0-6h) in normal mice, in addition to higher worm reduction with least inhibition of CYP450 and CYT b5 in EE2-infected mice. PZQ T3A, Bilharzid and Epiquantel showed, in addition to lower efficacy, higher K(el), lower t(1/2e), C(max) and AUC(0-6h). The 32-46% reduction of their bioavailability reflected on their antischistosomal efficacy and recovery of drug metabolizing enzymes. Quality of generic PZQ should include, in addition to examining the physicochemical characteristics of the brands, biological testing including efficacy and bioavailability studies.
Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, PO Box 30, Giza 12411, Egypt.
Sanaa
S
Botros
Naglaa
N
El-Lakkany
Sayed H
SH
Seif el-Din
Abdel-Nasser
AN
Sabra
Magda
M
Ibrahim
D000818:Animals; D000871:Anthelmintics / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D019540:Area Under Curve; D001682:Biological Availability; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D006207:Half-Life; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011223:Praziquantel / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012550:Schistosoma mansoni / Q000187:drug effects*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000378:metabolism / Q000469:parasitology
D000871:Anthelmintics; D011223:Praziquantel; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System