不同晶型的甲苯达唑对小鼠继发性细粒棘球蚴病的疗效比较(摘要)

Comparative Effectiveness of Mebendazole with Different Polymorphic Forms on Mice Infected with Secondary Cysts of Echinococcus granulosus

甲苯达唑(Meb)在不同或同一溶剂体系中,若改变其结晶条件可获得不同晶型的Meb,即MebⅠ、MebⅡ和MebⅢ晶型,与国外报道的MebB、C和A晶型相一致,一般认为,亚稳态晶型具有较好的生物活性,而Meb3种晶型的稳态性依次为Ⅲ>Ⅱ>Ⅰ。驱虫试验证明,Ⅰ和Ⅱ为有效晶型,而Ⅲ为无效晶型,故目前国内外均取MebⅡ型(即C型)供药用。本文系进一步观察Meb3种晶型对小鼠继发性细粒棘球蚴病的治疗作用。 小鼠于感染后5～8月用MebⅠ、MebⅡ或MebⅢ口服治疗,剂量为12.5和25mg·kg^(-1)·d(-1),连给14～28d对,MebⅠ和MebⅡ各组的平均囊重均明显小于对照组,MebⅢ各组的囊重则与对照组的相仿,但明显大于MebⅠ的各相应组。另一方面,尽管统计学上的差别不显著,但MebⅠ各组的平均囊重小于而囊重抑制率则高于MebⅡ的各相应组。 感染8个月的小鼠口服MebⅠ12.5或25mg·kg^(-1)·d^(-1),连给14d后,囊的生发层即示有不同程度的变化,且以剂量较大组为重。MebⅡ25mg·kg^(-1)组与MebⅠ相应组的相仿,但小剂量组的变化则较轻。当疗程延长至28d时,MebⅠ各组生发层的病变进一步加重。尤其25mg·kg^(-1)组,生发层示严重变化的占观察切面数的32.2％。MebⅡ组的生发层变化较MebⅠ相应组的为轻。感染小鼠口服MebⅢ12.5或25mg·kg^(-1)·d^(-1),连给

Mice infected with protoscoleces of Echinocococcus granulosus for 5-8 months were treated intragastrically with three different polymorphic forms of mebendaxole (Meb), e.g. form Ⅰ, Ⅱ and Ⅲ (Meb Ⅰ.Meb Ⅱ and Meb Ⅲ) at a daily dose of 12.5 or 25 mg.kg-1 for 14-28 days. Consequently, the mean cyst weight of the group treated with Meb Ⅰ or Meb Ⅱ was significantly less than that of the corresponding control, whereas no apparent effect of Meb Ⅲ on the cysts was observed. When mice were treated intragastrically with Meb Ⅰ, Meb n or Meb Ⅲ at a single dose of 25 mg.kg-1, the plasma concentration of the drug in Meb I group obtained from 0.5-16 hours after treatment were 0.5-2-fold and 10-17-fold higher than those of Meb Ⅱ and Meb Ⅲ groups, respectively. The drug-induced damage on the germinal layer of the cyst was more severe in Meb I groups and moderate in Meb Ⅱ groups. No apparent effect of Meb Ⅲ on the germinal layer was observed.