Dreyfuss G, Loiseau P, Wolf J G, Bories C, Gayral P, Nicolas J A
Laboratoire de Parasitologie, Faculté de Médecine de Limoges.
Bull Soc Pathol Exot Filiales. 1988;81(3 Pt 2):561-70.
Arsenical compounds are the main therapeutic way, effective in the neurological phase of trypanosomiasis. Unfortunately, their important toxicity prevents their easy administration. Structural cyclization of arsonic acid derivatives has led to a class of non-toxic compounds: spiroarsoranes. A 47 compound primary screening on an in vivo murine model of Trypanosoma brucei brucei resulted in the isolation of a very effective derivative after a single subcutaneous injection of 30 mg.kg-1 body weight (Chemotherapeutic Index = 21). In this study, trypanocidal activity of this compound was evaluated on an in vivo sheep model of trypanosomiasis by T. brucei brucei, according to experimental model of the Institute of Neurological Epidemiology and Tropical Neurology of Limoges (France). A single subcutaneous injection of 30 and 100 mg.kg-1 b.w., and 30 and 60 mg.kg-1 b.w. was given respectively during first and second phase of trypanosomiasis. Ovine pharmacokinetics of this compound will be evaluated in a further study.
砷化合物是治疗锥虫病神经期的主要治疗方法，效果显著。不幸的是，其严重的毒性使得给药不易。胂酸衍生物的结构环化产生了一类无毒化合物：螺砷烷。在布氏布氏锥虫的体内小鼠模型上对47种化合物进行初步筛选，单次皮下注射30 mg·kg-1体重后，分离出一种非常有效的衍生物（化疗指数 = 21）。在本研究中，根据法国利摩日神经流行病学与热带神经病学研究所的实验模型，在布氏布氏锥虫引起的锥虫病体内绵羊模型上评估了该化合物的杀锥虫活性。在锥虫病的第一阶段和第二阶段分别单次皮下注射30和100 mg·kg-1体重，以及30和60 mg·kg-1体重。该化合物的绵羊药代动力学将在进一步的研究中进行评估。
