Time and dose-dependence evaluation of nitroheterocyclic drugs for improving efficacy following Trypanosoma cruzi infection: A pre-clinical study

by Mazzeti AL, Diniz LDF, Gonçalves KR, Nascimento AFS, Spósito PAF, Mosqueira VCF, Machado-Coelho GLL, Ribeiro I, Bahia MT. Biochemical Pharmacology 2018, doi 10.1016/j.bcp.2018.01.005.

Summary: Benznidazole and nifurtimox-treatments regimens currently used in human are supported by very limited experimental data. This study was designed to evaluate the time and dose dependence for efficacy of the most important nitroheterocyclic drugs in use for Chagas disease – nifurtimox and benznidazole. The increased cure rates in T. cruzi infected animals that received nifurtimox for 40 days confirm the relationship between the length of treatment and efficacy, and an improvement in efficacy was observed with increasing benznidazole doses. Overall, these nonclinical study data provide evidence that the efficacy of benznidazole is dose and time dependent. These findings may be relevant for optimizing treatment of human Chagas disease.

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