title: 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: Cmax, 9.85 (2.73) and 10.63 (2.12) μg/mL; Tmax, 1.29 (0.58) and 1.33 (0.49) hours; and AUC0-12, 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 AUC0-12 (P < 0.001), AUC0-∞ (P = 0.002), area under the moment curve (AUMC) from 0 to 12 hours (P < 0.001), and AUMC0-∞ (P = 0.017). All CIs for the parameters measured were within the FDA-accepted limits of 80% to 125%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, Bangladesh.
authors.forename: Ashik
authors.initials: A
authors.lastname: Ullah
authors.affiliation: Department of Pharmaceutical Technology, University of Dhaka, Dhaka, Bangladesh.
authors.forename: Mohammad Abul Kalam
authors.initials: MA
authors.lastname: Azad
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, Bangladesh.
authors.forename: Rebeka
authors.initials: R
authors.lastname: Sultana
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, Bangladesh.
authors.forename: Maruf Mohammad
authors.initials: MM
authors.lastname: Akbor
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, Bangladesh.
authors.forename: Ahasanul
authors.initials: A
authors.lastname: Hasan
authors.affiliation: Institute of Statistical Research and Training, University of Dhaka, Dhaka, Bangladesh.
authors.forename: Mahbub
authors.initials: M
authors.lastname: Latif
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, Bangladesh.
authors.forename: Abul
authors.initials: A
authors.lastname: Hasnat
keywords: Bangladeshi population; amoxicillin; analysis of variance; bioequivalence; confidence interval; pharmacokinetic