Loiseau P M, Dreyfuss G, Doadrio L, Parrondo E, Craciunescu D G
Biologie et Contr l des Organismes Parasites, UPRES, Faculté de Pharmacie, Châtenay-Malabry, France.
J Chemother. 2001 Feb;13(1):59-65. doi: 10.1179/joc.2001.13.1.59.
Three organometallic complexes derived from pentamidine were evaluated for their trypanocidal effect on in vivo Trypanosoma brucei brucei models in comparison to pentamidine isethionate as reference compound. On the T. b.brucei mouse model, the most active compound was cis-platinum-pentamidine bromide. This compound was active when subcutaneously administered at the single dose of 1.5 micromol/kg and its chemotherapeutic index was 200 whereas pentamidine isethionate was active at 6 micromol/kg with a chemotherapeutic index of 13, when administered in the same conditions. Cis-platinum-pentamidine bromide was active at 1 mg/kg (1.44 mmoles/kg), in a single dose by subcutaneous route against the early stage of the T. b.brucei Antat 1-9 sheep model. Platinum kinetics in serum showed a Cmax of 0.2 mg/l reached 80 h after the treatment at this dose. Cis-platinum-pentamidine bromide, cis-platinum-pentamidine seleniocyanate, and cis-platinum-pentamidine thiocyanate were distributed in the deep compartment according to a monocompartmental model. In all cases, platinum was eliminated from the serum 700 hours post-treatment. All data obtained from these models show activity on the early stage of the disease and justify further investigations on the late stage of the disease.
对三种源自喷他脒的有机金属配合物进行了评估，以研究它们对体内布氏布氏锥虫模型的杀锥虫作用，并与作为参考化合物的乙磺酸盐喷他脒进行比较。在布氏布氏锥虫小鼠模型中，活性最强的化合物是顺铂 - 喷他脒溴化物。当以1.5微摩尔/千克的单剂量皮下给药时，该化合物具有活性，其化疗指数为200；而在相同条件下给药时，乙磺酸盐喷他脒在6微摩尔/千克时具有活性，化疗指数为13。顺铂 - 喷他脒溴化物在1毫克/千克（1.44毫摩尔/千克）时具有活性，通过皮下途径单剂量给药可对抗布氏布氏锥虫Antat 1 - 9绵羊模型的早期阶段。血清中的铂动力学显示，在该剂量治疗后80小时达到的最大浓度（Cmax）为0.2毫克/升。顺铂 - 喷他脒溴化物、顺铂 - 喷他脒硒氰酸盐和顺铂 - 喷他脒硫氰酸盐根据单室模型分布在深部隔室中。在所有情况下，治疗后700小时铂从血清中消除。从这些模型获得的所有数据表明该化合物对疾病早期具有活性，并证明有必要对疾病后期进行进一步研究。
