Bioequivalence evaluation of two capsule formulations of amoxicillin in healthy adult male bangladeshi volunteers: A single-dose, randomized, open-label, two-period crossover study

Abstract

Background : Amoxicillin, a semisynthetic penicillin antibiotic, is widely prescribed in Bangladesh due to its extended spectrum and its rapid and extensive oral absorption with good tolerability. Although a number of generic oral formulations of amoxicillin are available in Bangladesh, a study of the bioequivalence and pharmacokinetic properties of these formulations has not yet been conducted in a Bangladeshi population. Objective : The aim of this study was to assess the pharmacokinetic properties and bioequivalence of 2 formulations of amoxicillin 500-mg capsules (test, SK-mox ®; reference, Amoxil-Bencard ®) using serum data. Methods : This single-dose, randomized, open-label, 2-period crossover study was conducted in healthy male subjects in compliance with the Declaration of Helsinki and International Conference on Harmonisation guidelines. Subjects were assigned to receive the test or the reference drug as a single-dose, 500-mg capsule under fasting conditions after a 1-week washout period. After oral administration, blood samples were collected and analyzed for amoxicillin concentration using a validated high-performance liquid chromatography method. The pharmacokinetic parameters were determined using a noncompartmental method. The formulations were considered bioequivalent if the natural log-transformed ratios of pharmacokinetic parameters were within the predetermined equivalence range of 80% to 125%, according to the US Food and Drug Administration (FDA) requirement. Results : Twenty-four healthy adult male Bangladeshi volunteers (mean [SD] age, 26.92 [3.37] years; age range, 23–34 years; mean [SD] body mass index, 23.O9 [1.58] kg/m 2) participated in the study. Using serum data, the values obtained for the test and reference formulations, respectively, were as follows: C max, 9.85 (2.73) and 10.63 (2.12) μg/mL; T max, 1.29 (0.58) and 1.33 (0.49) hours; and AUC 0–12, 27.09 (7.62) and 28.56 (6.30) μg/mL · h −1. No period, sequence, or formulation effects were observed; however, significant variation was found among subjects with regard to AUC 0–12 ( P < 0.001), AUC 0−∞ ( P = 0.002), area under the moment curve (AUMC) from 0 to 12 hours ( P < 0.001), and AUMC 0−∞ ( P = 0.017). All CIs for the parameters measured were within the FDA-accepted limits of 80% to 125%. Conclusion : The present study suggests that the test 500-mg amoxicillin capsule was bioequivalent to the reference 500-mg capsule according to the FDA regulatory definition, in this population of healthy adult male Bangladeshi volunteers.