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Title: Pharmacokinetic and tissue distribution of benznidazole after oral administration in mice.
Authors: Melo, Luísa Helena Perin de
Silva, Rodrigo Moreira da
Fonseca, Kátia da Silva
Cardoso, Jamille Mirelle de Oliveira
Mathias, Fernando Augusto Siqueira
Reis, Levi Eduardo Soares
Molina, Israel
Oliveira, Rodrigo Corrêa de
Vieira, Paula Melo de Abreu
Carneiro, Cláudia Martins
Keywords: Chagas disease
Trypanosoma cruzi
Issue Date: 2017
Citation: MELO, L. H. P. et al. Pharmacokinetic and tissue distribution of benznidazole after oral administration in mice. Antimicrobial Agents and Chemotherapy, v. 61, p. e02410-16, 2017. Disponível em: <>. Acesso em: 29 ago. 2017.
Abstract: Specific chemotherapy using benznidazole (BNZ) for Chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. Although BNZ has been used to treat Chagas disease since the 1970s, few studies about the biodistribution of this drug exist. In this study, BNZ tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. A bioanalytical high-performance liquid chromatography method with a UV detector (HPLC-UV) was developed and validated according to the European Medicines Agency for quantification of BNZ in organs and plasma samples prepared by liquidliquid extraction using ethyl acetate. The developed method was linear in the BNZ concentration, which ranged from 0.1 to 100.0 g/ml for plasma, spleen, brain, colon, heart, lung, and kidney and from 0.2 to 100.0 g/ml for liver. Validation assays demonstrated good stability for BNZ under all conditions evaluated. Pharmacokinetic parameters confirmed rapid, but low, absorption of BNZ after oral administration. Biodistribution assays demonstrated different maximum concentrations in organs and similar times to maximum concentration and mean residence times, with means of 40 min and 2.5 h, respectively. Therefore, the biodistribution of BNZ is extensive, reaching organs such as the heart and colon, which are the most relevant organs affected by Trypanosoma cruzi infection, and also the spleen, brain, liver, lungs, and kidneys. Simultaneous analyses of tissues and plasma indicated high BNZ metabolism in the liver. Our results suggest that low bioavailability, instead of inadequate biodistribution, coul
ISSN: 1098-6596
Appears in Collections:DEACL - Artigos publicados em periódicos

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