title: Trypanocidal activity and platinum plasma kinetics of cis-Pt pentamidine iodide in Trypanosoma brucei sheep model.
abstract: 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.
authors.affiliation: Laboratoire de Parasitologie, Faculté de Pharmacie, Limoges Cedex, France.
authors.forename: G
authors.initials: G
authors.lastname: Dreyfuss
authors.forename: B
authors.initials: B
authors.lastname: Pénicaut
authors.forename: J A
authors.initials: JA
authors.lastname: Nicolas
authors.forename: D
authors.initials: D
authors.lastname: Craciunescu
authors.forename: P
authors.initials: P
authors.lastname: Loiseau
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007454:Iodides / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010419:Pentamidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D010984:Platinum / Q000097:blood; D012756:Sheep; D014018:Tissue Distribution; D014344:Trypanocidal Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D007454:Iodides; D009944:Organoplatinum Compounds; D014344:Trypanocidal Agents; C057919:platinum(II) pentamidine; D010984:Platinum; D010419:Pentamidine