Efficacy of Meglumine Antimoniate under Low Polymerization State Orally Administrated in Murine Model of Visceral Leishmaniasis.

Efficacy of Meglumine Antimoniate under Low Polymerization State Orally Administrated in Murine Model of Visceral Leishmaniasis. Antimicrob Agents Chemother. 2018 Jun 04;: Authors: Kato KC, de Morais-Teixeira E, Islam A, Leite MF, Demicheli C, de Castro WV, Corrêa-Junior JD, Rabello A, Frézard F Abstract Progress towards the improvement of meglumine antimoniate (MA) commercially known as Glucantime®, a highly effective but also toxic antileishmanial drug, has been hindered by the lack of knowledge and control on its chemical composition. Here, MA was manipulated chemically with the aim of achieving an orally effective drug. MA compounds were synthesized from either antimony pentachloride (MA-SbCl5) or potassium hexahydroxyantimonate (MA-KSb(OH)6) and prepared under low polymerization state. Those were compared to Glucantime® regarding chemical composition, permeation properties across cellulose membrane and Caco-2 cell monolayer and uptake by peritoneal macrophages. MA-SbCl5 and MA-KSb(OH)6 were characterized as less polymerized and more permeable 2:2 Sb-meglumine complexes, when compared to Glucantime® that consisted in a mixture of 2:3 and 3:3 Sb-meglumine complexes. The antileishmanial activity and hepatic uptake of all compounds were evaluated after oral administration in BALB/c mice infected with Leishmania infantum chagasi, as model of visceral leishmaniasis (VL). The synthetic MA compounds given at 300 mg Sb/kg/12h for 30...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research