Please use this identifier to cite or link to this item: http://www.repositorio.ufop.br/jspui/handle/123456789/13683
Title: Population pharmacokinetics and biodistribution of benznidazole in mice.
Authors: Melo, Luísa Helena Perin de
Pinto, Leonardo Santos Ribeiro
Nardotto, Glauco Henrique Balthazar
Fonseca, Kátia da Silva
Paiva, Beatriz Oliveira
Mendes, Thaís Fernanda Rodrigues Bastos
Molina, Israel
Oliveira, Rodrigo Corrêa de
Vieira, Paula Melo de Abreu
Carneiro, Cláudia Martins
Issue Date: 2020
Citation: MELO, L. H. P. de et al. Population pharmacokinetics and biodistribution of benznidazole in mice. Journal of Antimicrobial Chemotherapy, p. 2213-2221, 2020. Disponível em: <https://academic.oup.com/jac/article/75/8/2213/5827668>. Acesso em: 10 jun. 2021.
Abstract: Objectives: To evaluate the population pharmacokinetics of different benznidazole treatment regimens and the drug’s biodistribution in mice. Methods: Two hundred mice were divided into five groups according to benznidazole dosing regimens: (1) 100 mg/kg/day for 20 days; (2) 100 mg/kg/day for 40 days; (3) 200 mg/kg/day for 20 days; (4) 40 mg/kg/day for 20 days; or (5) 40 mg/kg/day for 40 days. The mice were euthanized and blood, heart, liver, colon and brain were collected. Samples were prepared by liquid-liquid extraction and analysed by HPLC-diode-array detection. The pharmacokinetic analysis of benznidazole was evaluated via non-linear mixed-effects modelling using the NONMEN program. Results: Our results demonstrate that mouse weight allometrically influences benznidazole clearance; the AUC curve and the highest plasma concentration are dose proportional; benznidazole does not influence its own metabolism; its tissue distribution is limited; and the standard treatment regimen for Chagas’ disease in mice (100 mg/kg/day for 20 days) is inadequate from a pharmacokinetic standpoint, as are the other regimens tested in this study (100 mg/kg/day for 40 days, 200 mg/kg/day for 20 days and 40 mg/kg/day for 20 or 40 days). Conclusions: Benznidazole reformulations that allow better tissue penetration and plasma and tissue exposure should be evaluated to enable higher cure rates in both animals and patients. The population pharmacokinetic model developed here can allow optimization of the dosing regimen of benznidazole to treat experimental Chagas’ disease. Determining appropriate treatment regimens in animals allows translation of these to clinical studies.
URI: http://www.repositorio.ufop.br/jspui/handle/123456789/13683
metadata.dc.identifier.uri2: https://academic.oup.com/jac/article/75/8/2213/5827668
metadata.dc.identifier.doi:  https://doi.org/10.1093/jac/dkaa130
ISSN: 1460-2091
Appears in Collections:DEACL - Artigos publicados em periódicos

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