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Published on: September 20, 2019
Comparative bioavailability of three benznidazole formulations in healthy individuals: a randomised study
Gabriel Parreiras Estolano da Silveira1,2, Laís Bastos da Fonseca1, Rita Estrela2,3,4
1Fundação Oswaldo Cruz-Fiocruz, Serviço de Equivalência e Farmacocinética, Rio de Janeiro, RJ, Brasil.
Background:
Benznidazole (BZN) has been used for more than fifty years in the treatment of Chagas disease (CD). It is produced by only three pharmaceutical companies worldwide: Lafepe (Brazil); Elea (Argentina) and Liconsa (Spain). The therapeutic interchangeability among these products has never been evaluated.
Objectives:
To assess bioequivalence between three 100 mg BZN formulations.
Methods:
Pharmaceutical equivalence, with dissolution testing, was assessed prior to the bioequivalence study. For bioequivalence, healthy adult participants received 100 mg of BZN formulations after meal, in a randomised clinical trial. Blood BZN concentrations were measured. Pharmacokinetic parameters were determined by non-compartmental analysis.
Findings:
The BZN Liconsa demonstrated faster in vitro dissolution. However, bioavailability was not different between formulations. The mean area under the curve (AUC)84h values were 49431.22 h*ng/mL (SD = 9938.53) to Lafepe, 48974.38 h*ng/mL (SD = 10304.67) to Elea and 48204.17 h*ng/mL (SD = 9342.18) to Liconsa. The mean Cmax values were 2339.23 ng/mL (SD = 445.53) for Lafepe, 2209.04 ng/mL (SD = 448.02) for Elea and 2303.90 ng/mL (SD = 431.41) for Liconsa. The mean tmax was not different between formulations. AUC were higher in women for Elea (20%) and Lafepe (27%). The adverse events did not differ between sexes.
Main Conclusions:
The 100 mg BZN formulations demonstrated bioequivalence.
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