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大环内酯类抗丝虫活性:伊维菌素、多拉菌素、米尔倍霉素A4肟和莫西菌素对库氏柔毛鼠感染卡氏罗阿丝虫、旋盘尾丝虫、马来布鲁线虫和彭亨布鲁线虫的比较研究

Antifilarial activity of macrocyclic lactones: comparative studies with ivermectin, doramectin, milbemycin A4 oxime, and moxidectin in Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi, and B. pahangi infection of Mastomys coucha.

作者信息

Schares G, Hofmann B, Zahner H

机构信息

Institute for Parasitology, Justus Liebig University Giessen, Germany.

出版信息

Trop Med Parasitol. 1994 Jun;45(2):97-106.

PMID:7939168
Abstract

The avermectins ivermectin and doramectin and the milbemycins milbemycin A4 oxime and moxidectin were tested for filaricidal activity in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi, and B. pahangi. Single subcutaneous doses of 0.005-5 mg/kg (L. carinii), 0.0005-0.5 mg/kg (A. viteae), 0.5 and 5 mg/kg (B. malayi), and 5 mg/kg (B. pahangi) were injected. Necropsies were performed 42 days after treatment. The avermectins caused a strong and rapid reduction of microfilaraemia in L. carinii and A. viteae infections within a few hours after treatment but showed only moderate efficacies on microfilariae of Brugia spp. The effects of the milbemycin derivatives on L. carinii and A. viteae microfilariae were generally weaker than those of the avermectins. However, moxidectin was comparatively active against microfilariae of Brugia spp. Subsequently the parasitaemia levels of L. carinii and A. viteae infected animals remained either almost completely depressed or tended to reincrease in a dose dependent manner whereas there was generally a continuous decrease of microfilaraemia levels in Brugia spp. infected animals. Adulticidal effects were limited to A. viteae although with neither dose of neither drug > 95% reductions of adult worm counts were reached. However, pathogenic influences of the drugs were observed on intrauterine embryonic stages of the parasites.

摘要

对伊维菌素、多拉菌素这两种阿维菌素以及米尔倍霉素A4肟和莫昔克丁进行了杀丝虫活性测试,受试对象为感染了卡氏住血丝线虫、罗阿罗阿丝虫、马来布鲁线虫和彭亨布鲁线虫的库氏多乳鼠。皮下注射单剂量0.005 - 5毫克/千克(针对卡氏住血丝线虫)、0.0005 - 0.5毫克/千克(针对罗阿罗阿丝虫)、0.5和5毫克/千克(针对马来布鲁线虫)以及5毫克/千克(针对彭亨布鲁线虫)。治疗后42天进行尸检。阿维菌素在治疗后数小时内,能使感染卡氏住血丝线虫和罗阿罗阿丝虫的小鼠体内微丝蚴血症显著且迅速减少,但对布鲁属微丝蚴的疗效仅为中等。米尔倍霉素衍生物对卡氏住血丝线虫和罗阿罗阿丝虫微丝蚴的作用通常比阿维菌素弱。然而,莫昔克丁对布鲁属微丝蚴具有相对较高的活性。随后,感染卡氏住血丝线虫和罗阿罗阿丝虫的动物体内寄生虫血症水平要么几乎完全降低,要么呈剂量依赖性地趋于再次升高,而感染布鲁属线虫的动物体内微丝蚴血症水平通常持续下降。成虫icidal作用仅限于罗阿罗阿丝虫,尽管两种药物的任何剂量均未使成虫计数减少超过95%。然而,观察到这些药物对寄生虫的子宫内胚胎阶段有致病性影响。

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