Witassek F, Burkhardt B, Eckert J, Bircher J
Eur J Clin Pharmacol. 1981;20(6):427-33. doi: 10.1007/BF00542095.
High oral doses of mebendazole have been only partly effective in the treatment of patients with alveolar or cystic echinococcosis. In order to improve therapeutic results the pharmacology of mebendazole has been investigated. Jirds experimentally infected with larval Echinococcus multilocularis were given food containing mebendazole 100 to 1000 ppm. Drug plasma concentrations above 0.25 mumol/l were associated with a reduction in parasite weight to 1 to 10% of that in untreated controls. In treated animals parasite weight was negatively correlated with the plasma mebendazole concentration and with the duration of therapy. In patients on long term therapy with similar doses of mebendazole (16 to 48 mg/kg per day), plasma concentrations were much lower than in jirds. Only 19% of fasting plasma concentrations exceeded 0.25 mumol/l. Plasma concentrations 4 h after the morning dose did not exceed this value in 48% of cases. The results can be explained by the irregular drug absorption and short plasma half life observed in 7 hospitalized patients. It is likely that better results would be obtained if doses of mebendazole were adjusted to produce peak plasma levels exceeding 0.25 mumol/l.
大剂量口服甲苯咪唑治疗肺泡型或囊型棘球蚴病患者时，疗效仅为部分有效。为提高治疗效果，对甲苯咪唑的药理作用进行了研究。给实验感染多房棘球绦虫幼虫的沙鼠喂食含100至1000 ppm甲苯咪唑的食物。血浆药物浓度高于0.25 μmol/L时，可使寄生虫重量降至未治疗对照组的1%至10%。在接受治疗的动物中，寄生虫重量与血浆甲苯咪唑浓度及治疗持续时间呈负相关。在接受类似剂量甲苯咪唑（每天16至48 mg/kg）长期治疗的患者中，血浆浓度远低于沙鼠。仅19%的空腹血浆浓度超过0.25 μmol/L。晨服后4小时，48%的患者血浆浓度未超过此值。7例住院患者药物吸收不规则且血浆半衰期短，可解释上述结果。若调整甲苯咪唑剂量使血浆峰值水平超过0.25 μmol/L，可能会取得更好的疗效。
