Pharmacokinetics of two pharmaceutical presentations of benznidazole in adult Trypanosoma cruzi infected population

Abstract

BACKGROUND Benznidazole (BNZ) is the primary treatment for Chagas disease. While pharmacokinetic studies of BNZ began in the 1970s, its metabolism and excretion are not fully understood. Alternatives like Benznidazol Lafepe® and Abarax® have replaced the original Radanil®. OBJECTIVES To compare the pharmacokinetic profiles of both currently available formulations of BNZ in adults with chronic Trypanosoma cruzi infection. METHODS The study involved 13 subjects each one receiving 100 mg of both presentations one week apart. Blood samples were collected over 48 hours post-administration to analyse BNZ concentration and calculate pharmacokinetic parameters. FINDINGS The analysis showed that both presentations had similar maximum plasma concentration and time to reach maximum plasma concentration values. Area under curve (AUC) values were slightly lower in Abarax® than Benznidazol Lafepe®. High intra-individual variability was observed, attributed to erratic absorption patterns with multiple peaks in concentration-time curves. The half-life values for both formulations were 9.1 and 8.0 h, respectively, with a significant intra-individual variability over 30%. MAIN CONCLUSIONS The mean difference in the AUC was lower than 10%, but exceeded the 90% confidence interval for the higher bioequivalence limit. Despite the high variability that confirms erratic absorption, the pharmacokinetic parameters of both formulations were within expected ranges.