Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, PO Box 30, Giza 12411, Egypt.
Exp Parasitol. 2011 Feb;127(2):515-21. doi: 10.1016/j.exppara.2010.10.019. Epub 2010 Oct 31.
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.
本研究调查了在埃及市售吡喹酮（PZQ）品牌与原纯品相比的疗效、生物利用度和主要参与其代谢的药物代谢酶。感染对 PZQ 敏感（CD）或不敏感（EE2）曼氏血吸虫分离株的小鼠被分为七组，其中六组接受 PZQ 品牌（Distocide、Epiquantel、Biltricide、Bilharzid、Praziquantel 和纯 PZQ），而第七组作为感染未处理的对照组。感染后 7 周，定量计算蠕虫数量，并检查肝 CYP450 和 CYT b5。进行 PZQ 药代动力学研究时，给正常小鼠分组给予不同的 PZQ 品牌，并分为亚组，在给药后 2、5、15、30、60、90、120、150、180、240 和 360 分钟时处死。物理化学检查显示，Biltricide、Distocide 和 PZQ T3A 的溶解速率优于 Epiquantel 和 Bilharzid。所有接受 PZQ 品牌治疗的小鼠组的蠕虫负担均显著下降，但 CD 分离株的效果优于 EE2 分离株。Biltricide 和 Distocide 显示正常小鼠的 C(max)和 AUC(0-6h)更高，此外，EE2 感染小鼠的 CYP450 和 CYT b5 抑制最小，蠕虫减少更多。PZQ T3A、Bilharzid 和 Epiquantel 除了疗效较低外，还表现出更高的 K(el)、更低的 t(1/2e)、C(max)和 AUC(0-6h)。它们的生物利用度降低 32-46%，反映在它们的抗血吸虫效果和药物代谢酶的恢复上。仿制药的质量除了要检查品牌的物理化学特性外，还应包括生物测试，包括疗效和生物利用度研究。
