title: Benzathine penicillin G: a model for long-term pharmacokinetic comparison of parenteral long-acting formulations.
abstract: OBJECTIVE
  Long-acting intramuscular penicillin G injection is an important product for the management of some severe infections. However, testing the bioequivalence of such long-acting formulations is difficult. Our aim was to undertake such a test using a generic formulation containing 1 200 000 IU of benzathine penicillin G powder and an innovator's product (Retarpen(®) 1·2 million units; Sandoz, Switzerland).
  
  
  METHODS
  In an open, double-blind, randomized, two-periods, two-group crossover study, 12 healthy male volunteers received both formulations of benzathine penicillin G on two different days with a 5-month washout period between the doses and a sampling period of over 500 h. A simple, sensitive and rapid high-performance liquid chromatography (HPLC)-UV method was developed and validated for determination of penicillin G plasma concentrations and other pharmacokinetic (PK) parameters.
  
  
  CONCLUSIONS
  The analytical method used produced linear responses within a wide analyte concentration range with average within-run and between-run variations of below 15% with acceptable recovery, accuracy and sensitivity. The primary PK parameters we used were maximum plasma concentration (Cmax ), time to reach the maximal concentration (Tmax ) and the area under the plasma concentration vs. time curve from time zero to the last sampling time (AUC0→t ) using a standard non-compartmental approach. Based on these parameters, the two formulations were bioequivalent.
  
  
  CONCLUSIONS
  We illustrate the bioequivalence testing of a very long-acting product. The data indicate that the generic test formulation and the branded reference formulation were bioequivalent in fasting healthy Iranian male volunteers.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: M A
authors.initials: MA
authors.lastname: Shahbazi
authors.forename: K
authors.initials: K
authors.lastname: Azimi
authors.forename: M
authors.initials: M
authors.lastname: Hamidi
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016568:Drugs, Generic / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D010401:Penicillin G Benzathine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D011208:Powders / Q000008:administration & dosage / Q000493:pharmacokinetics; D013557:Switzerland; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D016568:Drugs, Generic; D011208:Powders; D010401:Penicillin G Benzathine