Preclinical monitoring of drug association in experimental chemotherapy of Chagas’ disease by a new HPLC-UV method.
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2012
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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.
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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: <http://aac.asm.org/content/56/6/3344.long>. Acesso em: 10 jan. 2017.