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首页> 外文期刊>Journal of Parasitology >DRUG-METABOLIZING ENZYMES AND PRAZIQUANTEL BIOAVAILABILITY IN MICE HARBORING SCHISTOSOMA MANSONI ISOLATES OF DIFFERENT DRUG SUSCEPTIBILITIES
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DRUG-METABOLIZING ENZYMES AND PRAZIQUANTEL BIOAVAILABILITY IN MICE HARBORING SCHISTOSOMA MANSONI ISOLATES OF DIFFERENT DRUG SUSCEPTIBILITIES

机译：不同药物敏感性的小鼠血吸虫血吸虫分离株中药物代谢酶和吡喹酮的生物利用度

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The level of drug-metabolizing enzymes (cytochrome P450 [CYP450] and cytochrome b5 [cyt b5]) and the bioavailability of praziquantel (PZQ) were investigated in batches of mice infected with Schistosoma 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 2 groups. The first group was further subdivided into 5 subgroups. Subgroups 1 to 4 were treated 7 wk postinfection (PI) with oral PZQ at 25, 50, 100, and 200 mg/kg for 5 consecutive days, whereas the fifth subgroup was administered the vehicle only as control. Animals were perfused 9 wk PI, 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 and 200 mg/ kg PZQ. The second group was given PZQ 7 wk PI and was further subdivided into 11 subgroups, killed at 2, 5, 15, 30, 60, 90, 120, 150, 180, 240, and 360 min postdosing to study pharmacokinetic parameters of PZQ. Mice harboring S. mansoni isolates having higher PZQ ED50 (170.3 mg/kg for EE2 and 249.9 mg/kg for BANL vs. 82.96 mg/kg for CD) had higher levels of CYP450 and cyt b5, a PZQ Cmax decreased by 19–30% and area under the serum concentration-time curve0–6hr decreased by 57– 74%. Data 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.
机译：在曼氏血吸虫感染的小鼠中研究了药物代谢酶的水平（细胞色素P450 [CYP450]和细胞色素b5 [cyt b5]）和吡喹酮（PZQ）的生物利用度，显示对PZQ的敏感性降低（“ EE2”和“ BANL”分离物）或对药物的正常易感性（“ CD”分离物）。每一批分为两组。第一组进一步细分为5个子组。 1-4个小组在感染后第7周用口服PZQ分别以25、50、100和200 mg / kg的剂量治疗7周，连续5天，而第五个小组仅作为对照给予媒介物。给动物灌注9周的PI，并计数蠕虫以估计PZQ ED50。在感染的未处理小鼠以及用25和200 mg / kg PZQ处理的感染小鼠的肝微粒体中检查CYP450和cyt b5。第二组给予PZQ 7 wk PI，并进一步细分为11个亚组，在给药后2、5、15、30、60、90、120、150、180、240和360分钟杀死，以研究PZQ的药代动力学参数。携带曼氏沙门氏菌菌株的小鼠具有较高的PZQ ED50（EE2为170.3 mg / kg，BANL为249.9 mg / kg，而CD为82.96 mg / kg）具有较高的CYP450和cyt b5水平，PZQ Cmax降低19-30血药浓度-时间曲线下的百分比和面积0-6hr降低了57-74％。数据表明，对PZQ敏感性较低的曼氏链球菌分离物对肝药物代谢酶的抑制作用较低，因此PZQ的代谢转化率较高。

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