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Title: Benznidazole and Posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments.
Authors: Diniz, Lívia de Figueiredo
Urbina, Julio Alberto
Andrade, Isabel Mayer de
Mazzeti, Ana Lia
Martins, Tassiane Assíria Fontes
Caldas, Ivo Santana
Silva, André Talvani Pedrosa da
Ribeiro, Isabela
Bahia, Maria Terezinha
Keywords: Benznidazole
Trypanosoma cruzi
Issue Date: 2013
Citation: DINIZ, L. F. et al. Benznidazole and Posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments. PLoS Neglected Tropical Diseases, v. 7, p. e2367-e2377, 2013. Disponível em: <>. Acesso em: 08 nov. 2014.
Abstract: Background: Current chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with frequent side effects that can lead to treatment discontinuation. Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. We evaluated the efficacy of posaconazole in combination with benznidazole on Trypanosoma cruzi infection in vivo. Methods and Findings: Benznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. Using a rapid treatment protocol for 7 days, the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone, with the effects most evident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk) of benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses, indicating synergistic activity. Finally, sequential therapy experiments were carried out with benznidazole or posaconazole over a short interval (10 days), followed by the second drug administered for the same period of time. It was found that the sequence of benznidazole (100 mpk) followed by posaconazole (20 mpk) provided cure rates comparable to those obtained with the full (20 days) treatments with either drug alone, and no cure was observed for the short treatments with drugs given alone. Conclusions: Our data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds, and showed that combinations of benznidazole with posaconazole have a positive interaction in murine models of Chagas disease.
ISSN: 1932-6203
metadata.dc.rights.license: Nenhuma autorização é necessária para depósito dos artigos publicados pelos Periódicos PloS em repositório. Fonte: Plos <> Acesso em: 14 nov. 2014.
Appears in Collections:DECBI - Artigos publicados em periódicos

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