ABSTRACT
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.