Arzneimittelforschung 2012; 62(01): 18-21
DOI: 10.1055/s-0031-1295429
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

The Relative Bioavailability Study and Fasting and Fed States Pharmacokinetics of Bicalutamide 50-mg Tablets in Healthy Chinese Volunteers

H-M. Lu
1   Department of Oncology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, P. R. China
M. Ye
1   Department of Oncology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, P. R. China
› Author Affiliations
Further Information

Publication History

received 15 September 2011

accepted 03 November 2011

Publication Date:
10 January 2012 (online)


The aim of this study was to evaluate the bioequivalence of a new generic formulation of bicalutamide 50-mg tablets (test) and the available branded formulation (reference) to comply with regulatory criteria for marketing of the test product in China. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in 40 healthy male volunteers and consisted of separate fasting and fed phases. A single oral dose of the test or reference formulation was followed by a 6-week washout period, after which subjects received the alternative formulation. Blood samples were collected before dosing and at 0.5, 1, 2, 4, 8, 12, 15, 24, 30, 36, 48, 72, 144, 288, 432 and 576 h after dosing. Plasma samples were separated and assayed for bicalutamide using a selective and sensitive HPLC method with UV detection. The fasting and fed states pharmacokinetic parameters AUC0–576h, AUC0–∞, Cmax, tmax and t1/2 were determined from plasma concentration-time profile of both formulations. The formulations were considered bioequivalent when the 90% CIs of the geometric mean ratios (test:reference) for Cmax and AUC0–576h were within the regulatory range of 80–125%. There were no significant increases in bicalutamide Cmax, AUC0–576h or tmax for either formulation in the fed phase compared with the fasting phase. In both the fasting and fed portions of the study, the 90% CIs for the ratio (test:reference) of log-transformed Cmax and AUC0–576h were within the acceptance range for bioequivalence.

  • References

  • 1 Furr BJ. The development of Casodex (bicalutamide): Preclinical studies. Eur Urol. 1996; 29: 83-95
  • 2 Casodex [package insert]. Macclesfield, UK: AstraZeneca UK Ltd; 2009
  • 3 Heidenreich A, Aus G, Bolla M et al. EAU guidelines on prostate cancer. Eur Urol 2008; 53: 68-80
  • 4 Pfitzenmaier J, Altwein JE. Hormonal therapy in the elderly prostate cancer patient. Dtsch Ärztebl Int 2009; 106: 242-247
  • 5 Wirth MP, Hakenberg OW, Froehner M. Adjuvant hormonal treatment – the bicalutamide early prostate cancer program. Front Radiat Ther Oncol 2008; 41: 39-48
  • 6 Mukherjee A, Kirkovsky L, Yao XT et al. Enantioselective binding of Casodex to the androgen receptor. Xenobiotica 1996; 26: 117-122
  • 7 McKillop D, Boyle GW, Cockshott ID et al. Metabolism and enantioselective pharmacokinetics of Casodex in man. Xenobiotica 1993; 23: 1241-1253
  • 8 McKillop D, Simons PJ, Cockshott ID et al. Enantioselective metabolism and pharmacokinetics of Casodex in the male rat. Xenobiotica 1995; 25: 623-633
  • 9 Cockshott ID. Bicalutamide: Clinical pharmacokinetics and metabolism. Clin Pharmacokinet 2004; 43: 855-878
  • 10 Cockshott ID, Oliver SD, Young JJ et al. The effect of food on the pharmacokinetics of the bicalutamide (‘Casodex’) enantiomers. Biopharm Drug Dispos 1997; 18: 499-507
  • 11 Singh AK, Chaurasiya A, Jain GK et al. High performance liquid chromatography method for the pharmacokinetic study of bicalutamide SMEDDS and suspension formulations after oral administration to rats. Talanta 2009; 78: 1310-1314
  • 12 US Dept of Health and Human Services, Food and Drug Administration (FDA). Center for Drug Evaluation and Research (CDER). Guidance for Industry. Food-effect bioavailability and fed bioequivalence studies: Study design, data analysis, and labeling. Accessed October 3, 2008
  • 13 World Health Organization (WHO). Working document QAS/04.093/Rev.4. Multisource (generic) pharmaceutical products: Guidelines on registration requirements to establish interchangeability. Draft revision. prep/QAS04_093Rev4_final.pdf Accessed October 3, 2008
  • 14 Lee S, Chung YJ, Kim BH et al. Comparative pharmacokinetic evaluation of two formulations of bicalutamide 50-mg tablets: an open-label, randomized-sequence, single-dose, two-period crossover study in healthy Korean male volunteers. Clin Ther 2009; 31: 3000-3008
  • 15 Welling PG. Interactions affecting drug absorption. Clin Pharm 1984; 9: 404-434
  • 16 Welling PG. Effects of food on drug absorption. Pharmacol Ther 1989; 43: 425-441