Time and dose-dependence evaluation of nitroheterocyclic drugs for improving efficacy following Trypanosoma cruzi infection: A pre-clinical study
| Autor: | Álvaro Fernando da Silva do Nascimento, Maria Terezinha Bahia, Pollyanna Álvaro Spósito, Karolina R. Gonçalves, Isabela Ribeiro, Lívia de Figueiredo Diniz, Vanessa Carla Furtado Mosqueira, Ana Lia Mazzeti, George Luiz Lins Machado-Coelho |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chagas disease Trypanosoma cruzi 030106 microbiology Drug Resistance Dose dependence Drug resistance Pharmacology Parasitemia Biochemistry Drug Administration Schedule Clinical study Mice 03 medical and health sciences medicine Animals Chagas Disease Nifurtimox Dose-Response Relationship Drug biology business.industry medicine.disease biology.organism_classification Trypanocidal Agents Benznidazole business medicine.drug |
| Zdroj: | Biochemical Pharmacology. 148:213-221 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/j.bcp.2018.01.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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