Please use this identifier to cite or link to this item:
Title: Preclinical monitoring of drug association in experimental chemotherapy of Chagas’ disease by a new HPLC-UV method.
Authors: Silva, Ricardo Moreira da
Oliveira, Líliam Teixeira
Barcellos, Neila Marcia Silva
Souza, Jacqueline de
Lana, Marta de
Issue Date: 2012
Citation: SILVA, R. M. da et al. Preclinical monitoring of drug association in experimental chemotherapy of Chagas’ disease by a new HPLC-UV method. Antimicrobial Agents and Chemotherapy , v. 56, p. 3344-3348, 2012. Disponível em: <>. Acesso em: 10 jan. 2017.
Abstract: A combination of drugs in experimental chemotherapy of Chagas’ disease may increase the effectiveness of treatment. To evaluate the possible mechanisms that influence the improvement of therapy, we investigated the pharmacokinetic interaction between benznidazole and itraconazole in a murine model treated orally with single doses of 5 mg of each compound separately or together. Blood samples from treated mice were collected at different intervals for 48 h, and a high-performance liquid chromatography (HPLC)-UV method was used to quantify both drugs in the plasma. A decrease of 1.5-fold in the maximum drug concentration in the plasma (Cmax) and an increase of 2.66-fold in the volume of distribution (V) and 7.5-fold in the elimination half-life (t1/2 ) of benznidazole when coadministered with itraconazole were observed. The parameters area under the curve (AUC0-t), area under the curve extrapolated to infinity (AUC0- ), time to maximum concentration of drug in serum (Tmax), and clearance (CL) for benznidazole were not significantly different in this therapeutic regime. None of the evaluated parameters for ITC demonstrated a significant difference between isolated and associated administration. These results suggest that the main effect of this interaction leads to accumulation of benznidazole in the biological system. This effect may contribute to the improved therapeutic efficacy of this combination of drugs, in addition to synergism of the different mechanisms of action of benznidazole and itraconazole against Trypanosoma cruzi in vivo.
ISSN: 1098-6596
Appears in Collections:DEFAR - Artigos publicados em periódicos

Files in This Item:
File Description SizeFormat 
ARTIGO_PreclinicalMonitoringDrug.pdf328,63 kBAdobe PDFView/Open    Request a copy

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.