title: Pharmacokinetic comparison of 2 formulations of anastrozole (1 mg) in healthy Korean male volunteers: a randomized, single-dose, 2-period, 2-sequence, crossover study.
abstract: BACKGROUND
  Anastrozole is an aromatase inhibitor used to treat advanced breast cancer in postmenopausal women. A generic 1-mg tablet of anastrozole was recently developed.
  
  
  OBJECTIVE
  The study was designed to provide data to submit to Korean regulatory authorities to allow marketing of the test formulation. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy male adult volunteers.
  
  
  METHODS
  This single-dose, randomized, double-blind, 2-way crossover trial was conducted in the Clinical Trial Center at the Asan Medical Center (Seoul, Korea). A total of 24 healthy male Korean volunteers were enrolled. Subjects were randomized to receive 1 mg of the test or reference formulation, and pharmacokinetic (PK) parameters were measured. After a 3-week washout period, the other formulation was administered, and PK parameters were measured again. C(max) and AUC(last) were determined from blood samples obtained at 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours after drug administration. The formulations were considered bioequivalent if the 90% CIs of the geometric mean ratios of test-to-reference formulations for AUC(last) and C(max) were within the bioequivalence limits of 0.8 to 1.25. Nonlinear mixed-effect modeling and Monte Carlo simulations for both formulations were also conducted, and the results were used to characterize and compare the PK properties. Safety profile and tolerability were assessed using measurements of vital signs, clinical chemistry tests, and interviews.
  
  
  RESULTS
  All enrolled subjects completed the study. A total of 8 adverse events (AEs) were reported (2 on test formulation, 6 on reference formulation) in 7 of 24 participants. These AEs were headache (n = 1), hordeolum (n = 1), and abnormal laboratory test values (n = 6). Both formulations were well tolerated, and there were no serious AEs. Both formulations were best described by a 2-compartment disposition model with lag phase. The 90% CIs of the geometric mean ratios of test formulation to reference formulation were 0.96 to 1.08 for C(max) and 0.93 to 1.0 for AUC(last).
  
  
  CONCLUSIONS
  The test and reference formulations had similar PK parameters and similar plasma concentration-time profiles. The test formulation of anastrozole met the Korean regulatory criteria (AUC and C(max)) for assuming bioequivalence. ClinicalTrials.gov identifier: NCT01105299.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Korea.
authors.forename: Yook-Hwan
authors.initials: YH
authors.lastname: Noh
authors.forename: Young-Ju
authors.initials: YJ
authors.lastname: Ko
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Jong-Lyul
authors.initials: JL
authors.lastname: Ghim
authors.forename: Sangmin
authors.initials: S
authors.lastname: Choe
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Jung
authors.forename: Un-Jib
authors.initials: UJ
authors.lastname: Kim
authors.forename: Seok-Joon
authors.initials: SJ
authors.lastname: Jin
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Geun-Seog
authors.initials: GS
authors.lastname: Song
authors.forename: Hyeong-Seok
authors.initials: HS
authors.lastname: Lim
authors.forename: Kyun-Seop
authors.initials: KS
authors.lastname: Bae
mesh_terms: D000328:Adult; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole