Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole

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 cruzi quantitative 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.

Ratio of plasma benznidazole (BNZ) concentration (mg/L)/BNZ administered dose (mg/Kg/d) during steady state phase. Patient 1 had two samples per day from three different days showed a high ratio of BNZ concentration all the times (1/1: patient 1, samples day 1; 1/2: patient 1, samples day 2; 1/3: patient 1, samples day 3). Patient 2 took half the indicated dose, her plasma drug concentration was normalised according to BNZ administered dose, and presented similar ratio as the rest of the patients of the series (patients 3, 4, 5, and 6).