title: Bioequivalence of 2 azithromycin capsule formulations: a randomized, single-dose, open-label, 2-period crossover study in healthy male pakistani volunteers.
abstract: BACKGROUND
  Approximately 68 brands of azithromycin capsule formulations are available in Pakistan; however, published data on their bioequivalence in the Pakistani population are not available.
  
  
  OBJECTIVE
  Upon instructions from and approval of the Ministry of Health, Pakistan, this study was designed to evaluate the bioequivalence of a locally manufactured azithromycin capsule formulation with a reference formulation from a multinational manufacturer. This study compared dissolution profiles, relative bioavailability, and other pharmacokinetic parameters of the 2 formulations.
  
  
  METHODS
  A single oral 500-mg dose of the 2 formulations was administered to 12 healthy adult Pakistani male volunteers under fasting conditions in a randomized, open-label, 2-period crossover study. The trial included collection of blood samples over 48 hours and a 2-week washout period. Azithromycin serum concentrations were quantified using a validated RP-HPLC/ultraviolet (UV) detection method. These results were used to determine the intended pharmacokinetic parameters. As mandated by the US Food and Drug Administration and the European Medicine Agency, the test and reference formulations were considered bioequivalent if the 90% CIs of the geometric mean ratios for the log-transformed values of their pharmacokinetic parameters were within the predetermined range of 0.8 to 1.25.
  
  
  RESULTS
  When subjected to a simple model independent approach of dissolution profile comparison, f 1 (difference) and f 2 (similarity factor) were found to be 5.47 and 70.04, respectively. Similarly, the 2 azithromycin capsule formulations were well tolerated by all volunteers. Low %CV of the pharmacokinetic parameters at a sample size of 12 and significance level of 0.05 contributed to acceptable (>0.8) power of the test. The 90% CIs for the ratios of Cmax, AUC0-48, Tmax, t1/2, and mean residence time, respectively, were 0.83-0.93, 0.85-1.10, 0.86-1.08, 0.92-1.17, and 0.92-1.16.
  
  
  CONCLUSIONS
  This single-dose study found that test and reference formulations met the regulatory criteria for bioequivalence in these fasted, healthy male Pakistani volunteers.
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
authors.lastname: Samiullah
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
authors.forename: Zafar
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
authors.forename: Abbas
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
authors.forename: Abad
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
authors.forename: Yasar
authors.initials: Y
authors.lastname: Shah
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
authors.forename: Lateef
authors.initials: L
authors.lastname: Ahmad
keywords: RP-HPLC/UV detection method; azithromycin; bioequivalence; human serum; pharmacokinetics; quantification