Time and dose-dependence evaluation of nitroheterocyclic drugs for improving efficacy following Trypanosoma cruzi infection : a pre-clinical study.
No Thumbnail Available
Date
2018
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
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. In order to evaluate time dependence,
Y strain-infected mice received benznidazole for a total of 1, 3, 7, 10, 20, and 40 days.
Treatment courses of 3–10-day were effective in clearing parasitaemia and suppressing mortality, but
parasitological cure was not achieved. Extending the treatments to 20 or 40 days clearly improved benznidazole
efficacy. The 20-day treatment induced cure in 57.1% of Y strain infections (partially drug resistant)
but failed to cure Colombian strain infections (full drug resistant), while the 40-day treatment
resulted in cure of 100% of Y and 50% of Colombian strain infected mice. 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. An improvement in efficacy was observed with increasing benznidazole doses;
cure was verified in 28.6% (75 mg/kg), 57.1% (100 mg/kg) and 80% (300 mg/kg). 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.
Description
Keywords
Trypanosoma cruzi, Benznidazole, Chagas disease chemotherapy, Nitroheterocyclic drugs
Citation
MAZZETI, A. L. et al. Time and dose-dependence evaluation of nitroheterocyclic drugs for improving efficacy following Trypanosoma cruzi infection : a pre-clinical study. Biochemical Pharmacology, v. 148, p. 213-221, 2018. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0006295218300054?via%3Dihub>. Acesso em: 05 abr. 2018.