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

两种苯硝唑药物制剂在成年克氏锥虫感染人群中的药代动力学研究

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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.

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