Antitrypanosomal properties of cis-platinum-pentamidine bromide, thiocyanate and seleniocyanate on Trypanosoma brucei brucei mouse and sheep models

Three organometallic complexes derived from pentamidine were evaluated for their trypanocidal effect on in vivo Trypanosoma brucei brucei models in co mparison to pentamidine isethionate as reference compound. On the T.b.bruce i mouse model, the most active compound was cis-platinum-pentamidine bromid e. This compound was active when subcutaneously administered at the single dose of 1.5 mu mol/kg and its chemotherapeutic index was 200 whereas pentam idine isethionate was active at 6 mu mol/kg with a chemotherapeutic index o f 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.bru cei Antat 1-9 sheep model. Platinum kinetics in serum showed a C-max 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 compa rtment according to a monocompartmental model. In all cases, platinum was e liminated from the serum 700 hours post-treatment. All data obtained from t hese models show activity on the early stage of the disease and justify fur ther investigations on the late stage of the disease.