Pharmacokinetic and tissue distribution of benznidazole after oral administration in mice.
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2017
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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
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Chagas disease, Trypanosoma cruzi
Citação
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: <http://aac.asm.org/content/61/4/e02410-16.long>. Acesso em: 29 ago. 2017.