Benznidazole and Posaconazole in Experimental Chagas Disease: Positive Interaction in Concomitant and Sequential Treatments
Abstract
In this study, we investigated the efficacy of posaconazole in combination with benznidazole against Trypanosoma cruzi acute infections in mice, to support the potential clinical evaluation of such combination therapy for Chagas disease. The curative action of benznidazole/posaconazole combinations was explored in an established acute infection model with the Y strain in which benznidazole and posaconazole treatments induced a 70% and 80% cure rate, respectively, when administered alone at optimal doses. When tested in combination, a 80% to 90% cure rate was detected in mice receiving 25, 50 or 75 mpk of benznidazole, plus 5 or 10 mpk of posaconazole, while treatment with the sub-optimal doses of the drugs given alone induced only 0–43% cures, indicating synergistic effects. Finally, sequential short (10 days) treatments with benznidazole (100 mpk) followed by posaconazole (20 mpk) led to an 80% cure rate, comparable with full-length treatments with either drug given alone, while no cures were observed for short treatments with single drugs. Our results demonstrate that it is possible to achieve the same or better therapeutic effect using lower dosages of posaconazole and benznidazole in combination, decreasing treatment costs and potential toxicity.
Citation
de Figuerido Diniz, L.; Urbina, J.A.; Mayer de Andrade, I.; Mazzeti, A.L.; Martins, T.A.F.; Santana Caldes, I.; Talvani, A.; Ribeiro, I.; Bahia, M.T. Benznidazole and Posaconazole in Experimental Chagas Disease: Positive Interaction in Concomitant and Sequential Treatments. PLoS Neglected Tropical Diseases (2013) 7 (8) e2367. [DOI: 10.1371/journal.pntd.0002367]