PMID- 22281018
OWN - NLM
STAT- MEDLINE
DCOM- 20120622
LR  - 20181201
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 34
IP  - 2
DP  - 2012 Feb
TI  - Pharmacokinetic comparison of 2 formulations of anastrozole (1 mg) in healthy 
      Korean male volunteers: a randomized, single-dose, 2-period, 2-sequence, 
      crossover study.
PG  - 305-13
LID - 10.1016/j.clinthera.2012.01.008 [doi]
AB  - 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). CONCLUSION: 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.
CI  - Copyright (c) 2012 Elsevier HS Journals, Inc. All rights reserved.
FAU - Noh, Yook-Hwan
AU  - Noh YH
AD  - Department of Clinical Pharmacology and Therapeutics, College of Medicine, 
      University of Ulsan, Asan Medical Center, Seoul, Korea.
FAU - Ko, Young-Ju
AU  - Ko YJ
FAU - Cho, Sang-Heon
AU  - Cho SH
FAU - Ghim, Jong-Lyul
AU  - Ghim JL
FAU - Choe, Sangmin
AU  - Choe S
FAU - Jung, Jin Ah
AU  - Jung JA
FAU - Kim, Un-Jib
AU  - Kim UJ
FAU - Jin, Seok-Joon
AU  - Jin SJ
FAU - Park, Hyun-Jung
AU  - Park HJ
FAU - Song, Geun-Seog
AU  - Song GS
FAU - Lim, Hyeong-Seok
AU  - Lim HS
FAU - Bae, Kyun-Seop
AU  - Bae KS
LA  - eng
SI  - ClinicalTrials.gov/NCT01105299
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120126
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (Nitriles)
RN  - 0 (Triazoles)
RN  - 2Z07MYW1AZ (Anastrozole)
SB  - IM
MH  - Adult
MH  - Anastrozole
MH  - Aromatase Inhibitors/*pharmacokinetics
MH  - Chemistry, Pharmaceutical
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nitriles/administration & dosage/adverse effects/*pharmacokinetics
MH  - Triazoles/administration & dosage/adverse effects/*pharmacokinetics
EDAT- 2012/01/28 06:00
MHDA- 2012/06/23 06:00
CRDT- 2012/01/28 06:00
PHST- 2011/11/23 00:00 [received]
PHST- 2011/12/13 00:00 [revised]
PHST- 2012/01/03 00:00 [accepted]
PHST- 2012/01/28 06:00 [entrez]
PHST- 2012/01/28 06:00 [pubmed]
PHST- 2012/06/23 06:00 [medline]
AID - S0149-2918(12)00009-4 [pii]
AID - 10.1016/j.clinthera.2012.01.008 [doi]
PST - ppublish
SO  - Clin Ther. 2012 Feb;34(2):305-13. doi: 10.1016/j.clinthera.2012.01.008. Epub 2012 
      Jan 26.