ABSTRACT
Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruziquantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Chagas Disease/drug therapy , Nitroimidazoles/pharmacokinetics , Trypanocidal Agents/pharmacokinetics , Trypanosoma cruzi/drug effects , Chemistry, Pharmaceutical , Chagas Disease/metabolism , Follow-Up Studies , Nitroimidazoles/administration & dosage , Nitroimidazoles/blood , Real-Time Polymerase Chain Reaction , Trypanocidal Agents/administration & dosage , Trypanocidal Agents/blood , Trypanosoma cruzi/isolation & purificationABSTRACT
Benznidazole (Bz) exhibits toxic side effects in animal studies and clinical use. Reductive metabolism of Bz in liver microsomes modulates the duration of its chemotherapeutic effect and its toxicity. The rate of this metabolism depends on age and is less intense in newborns and youngsters than in adults. In the present study, we determined Bz blood levels in rats of different ages that received Bz intragastrically (100 mg/kg). We developed and validated a high-pressure liquid chromatography with UV detector method for determination of Bz levels in whole blood. Bz levels were significantly higher and persisted for longer periods of time in the blood of young rats when compared to that of adult animals.