Dreyfuss G, Pénicaut B, Nicolas J A, Craciunescu D, Loiseau P
Laboratoire de Parasitologie, Faculté de Pharmacie, Limoges Cedex, France.
Trop Med Parasitol. 1993 Jun;44(2):95-8.
The trypanocidal properties of cis-Pt pentamidine iodide have been studied on the T. b. brucei sheep model. The compound was evaluated on the lymphatic-plasma phase of the disease and appeared to be active on the circulating parasites. Cis-Pt pentamidine iodide was active at 5 mgl.kg-1 in one single dose both in mouse and sheep trypanosomiasis models. The chemotherapeutic index was about 200 in the mouse. As we observed previously with the chloride derivative, platinum plasma values for cis-Pt pentamidine iodide were rather constant between 24 and 48 hours. The nature of the salt associated to cis-Pt pentamidine had a direct effect on the compound kinetics. The iodide compound was distributed quickly and largely within deep compartments according to a monocompartmental model. The theoretical volume of distribution was 6.41.kg-1 for a 100% absorbed fraction. The two iodide ions of the complex probably played an important role in the compound kinetics mainly due to the extended release effect. The iodide salt of cis-Pt pentamidine could therefore be used in chemoprophylaxis of African trypanosomiasis.
已在布氏布氏锥虫绵羊模型上研究了顺铂喷他脒碘化物的杀锥虫特性。该化合物在疾病的淋巴 - 血浆期进行了评估，似乎对循环中的寄生虫有活性。顺铂喷他脒碘化物在小鼠和绵羊锥虫病模型中以5mg/kg的单次剂量具有活性。在小鼠中，化疗指数约为200。正如我们之前对氯化物衍生物所观察到的那样，顺铂喷他脒碘化物的血浆铂值在24至48小时之间相当恒定。与顺铂喷他脒相关的盐的性质对化合物动力学有直接影响。碘化物化合物根据单室模型在深部隔室中快速且大量分布。对于100%吸收分数，理论分布体积为6.41L/kg。配合物的两个碘离子可能在化合物动力学中起重要作用，主要是由于缓释效应。因此，顺铂喷他脒碘化物盐可用于非洲锥虫病的化学预防。
