Efficacy of Meglumine Antimoniate in a Low Polymerization State Orally Administered in a Murine Model of Visceral Leishmaniasis

dc.creatorKato, Kelly Cristina
dc.creatorTeixeira, Eliane de Morais
dc.creatorIslam, Arshad
dc.creatorLeite, Maria de Fatima
dc.creatorDemicheli, Cynthia
dc.creatorCastro, Whocely Victor de
dc.creatorCorrêa Junior, José Dias
dc.creatorRabello, Ana Lucia Teles
dc.creatorFrezard, Frederic Jean Georges
dc.date2019-08-12T15:53:18Z
dc.date2019-08-12T15:53:18Z
dc.date2018
dc.date.accessioned2023-09-27T00:15:29Z
dc.date.available2023-09-27T00:15:29Z
dc.identifierKATO, Kelly Cristina et al. Efficacy of Meglumine Antimoniate in a Low Polymerization State Orally Administered in a Murine Model of Visceral Leishmaniasis. Antimicrob Agents Chemother, v. 62, n. 8, p. 1-10, 2018.
dc.identifier0066-4804
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/34735
dc.identifier10.1128/AAC.00539-18
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8899034
dc.descriptionProgress toward 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 of 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 a low polymerization state. These compounds were compared to Glucantime regarding chemical composition, permeation properties across a 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 permeative 2:2 Sb-meglumine complexes than Glucantime, which consisted of a mixture of 2:3 and 3:3 Sb-meglumine complexes. The antileishmanial activities and hepatic uptake of all compounds were evaluated after oral administration in BALB/c mice infected with Leishmania infantum chagasi, as a model of visceral leishmaniasis (VL). The synthetic MA compounds given at 300 mg Sb/kg of body weight/12 h for 30 days significantly reduced spleen and liver parasite burdens, in contrast to those for Glucantime at the same dose. The greater activity of synthetic compounds could be attributed to their higher intestinal absorption and accumulation efficiency in the liver. MA-SbCl5 given orally was as efficacious as Glucantime by the parenteral route (80 mg Sb/kg/24 h intraperitoneally). These data taken together suggest that treatment with a less-polymerized form of MA by the oral route may be effective for the treatment of VL.
dc.description2100-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsrestricted access
dc.subjectLeishmania infantum
dc.subjectAntimony
dc.subjectChemotherapy
dc.subjectLeishmaniasis
dc.subjectMeglumine antimoniate
dc.subjectOral route
dc.titleEfficacy of Meglumine Antimoniate in a Low Polymerization State Orally Administered in a Murine Model of Visceral Leishmaniasis
dc.typeArticle


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