Abstract
Purpose
Abiraterone acetate (AA) was recently approved for castration-resistant prostate cancer in Japan. Two phase 1 studies were conducted to assess the pharmacokinetics of abiraterone after single-dose administration in Japanese healthy men and to evaluate the effects of food timing on abiraterone pharmacokinetics after single-dose administration of AA in Japanese and Caucasian healthy men.
Methods
In the dose-proportionality study, subjects (n = 30 Japanese) were randomly assigned to receive single doses of 250, 500, and 1,000 mg AA, and in the food-timing study, subjects (n = 22 Japanese and n = 23 Caucasian) randomly received single doses of 1,000 mg AA under fasted (overnight) and three different modified fasting conditions.
Results
Mean C max and AUC∞ for abiraterone increased dose-dependently in Japanese healthy men; however, 90 % confidential interval (CI) was outside the predefined dose-proportionality criteria. Based on geometric mean ratios and 90 % CIs (versus overnight fasting condition), abiraterone exposure (AUC) increased significantly with dosing 1 h premeal, 2 h postmeal, or in between two meals 4 h apart by 57 %, 595 %, and 649 %, respectively.
Conclusion
No clinically meaningful difference was observed in the pharmacokinetics of abiraterone between Caucasian and Japanese subjects.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Siegel R, Naishadham D, Jemal A (2013) Cancer statistics. CA: Cancer J Clin 63(1):11–30. doi:10.3322/caac.21166
Cullen J, Elsamanoudi S, Brassell SA, Chen Y, Colombo M, Srivastava A, McLeod DG (2012) The burden of prostate cancer in Asian nations. J carcinog 11:7. doi:10.4103/1477-3163.94025
Namiki M, Akaza H, Lee SE, Song JM, Umbas R, Zhou L, Lee BC, Cheng C, Chung MK, Fukagai T, Hinotsu S, Horie S (2010) Prostate cancer working group report. Jpn J Clin Oncol 40(Suppl 1):i70–i75. doi:10.1093/jjco/hyq130
Kawahara T, Miyoshi Y, Sekiguchi Z, Sano F, Hayashi N, Teranishi J, Misaki H, Noguchi K, Kubota Y, Uemura H (2012) Risk factors for metastatic castration-resistant prostate cancer (CRPC) predict long-term treatment with docetaxel. PLoS ONE 7(10):e48186. doi:10.1371/journal.pone.0048186
Nishimura K, Nonomura N, Hashine K, Kanayama HO, Ozono S, Miura T, Miki T, Kakehi Y, Arai Y, Ogawa O, Fujita R, Nonomura K, Mizokami A, Hoshi S, Akaza H (2013) Prolonged treatment with three-weekly docetaxel plus daily prednisolone for metastatic castration-resistant prostate cancer: a multicenter, phase II, open-label, non-comparative, extension study in Japan. Int J Clin Oncol 18(2):306–313. doi:10.1007/s10147-012-0380-1
Suzuki K (2009) Epidemiology of prostate cancer and benign prostatic hyperplasia. Jpn Med Assoc J 52:478–483
de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI, Investigators C-A- (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21):1995–2005. doi:10.1056/NEJMoa1014618
Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE, Investigators C-A- (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368(2):138–148. doi:10.1056/NEJMoa1209096
Acharya M, Bernard A, Griffin T et al (2011) A phase 1 study to determine the effect of food on the pharmacokinetics of abiraterone acetate (AA) in healthy male subjects. Meeting abstract. In: The annual meeting of American association of pharmaceutical scientists, Washington, DC, 23–27 Oct 2011
LE Marbury T, Stonerock R et al (2014) Single-dose pharmacokinetic studies of abiraterone acetate in men with hepatic or renal impairment. J Clin Pharmacol 54(7):732–741
Acharya M, Bernard A, Gonzalez M, Jiao J, De Vries R, Tran N (2012) Open-label, phase I, pharmacokinetic studies of abiraterone acetate in healthy men. Cancer Chemother Pharmacol 69(6):1583–1590. doi:10.1007/s00280-012-1865-3
Tolcher AW, Chi KN, Shore ND, Pili R, Molina A, Acharya M, Kheoh T, Jiao JJ, Gonzalez M, Trinh A, Pankras C, Tran N (2012) Effect of abiraterone acetate plus prednisone on the QT interval in patients with metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol 70(2):305–313. doi:10.1007/s00280-012-1916-9
Attard G, Reid AH, Yap TA, Raynaud F, Dowsett M, Settatree S, Barrett M, Parker C, Martins V, Folkerd E, Clark J, Cooper CS, Kaye SB, Dearnaley D, Lee G, de Bono JS (2008) Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 26(28):4563–4571. doi:10.1200/JCO.2007.15.9749
Ryan CJ, Smith MR, Fong L, Rosenberg JE, Kantoff P, Raynaud F, Martins V, Lee G, Kheoh T, Kim J, Molina A, Small EJ (2010) Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol 28(9):1481–1488. doi:10.1200/JCO.2009.24.1281
Saruwatari J, Yasui-Furukori N, Inoue Y, Kaneko S (2010) Effect of dose timing in relation to food intake on systemic exposure to blonanserin. Eur J Clin Pharmacol 66(9):899–902. doi:10.1007/s00228-010-0834-1
Derks M, Kawamura H, Abt M, Meneses-Lorente G, Phelan M, Ishikawa T (2011) Effects of food intake on the pharmacokinetic properties of dalcetrapib: findings from three phase I, single-dose crossover studies in healthy volunteers. Clin Ther 33(6):754–765. doi:10.1016/j.clinthera.2011.05.046
Pithavala YK, Chen Y, Toh M, Selaru P, LaBadie RR, Garrett M, Hee B, Mount J, Ni G, Klamerus KJ, Tortorici MA (2012) Evaluation of the effect of food on the pharmacokinetics of axitinib in healthy volunteers. Cancer Chemother Pharmacol 70(1):103–112. doi:10.1007/s00280-012-1888-9
Singh BN (1999) Effects of food on clinical pharmacokinetics. Clin Pharmacokinet 37(3):213–255. doi:10.2165/00003088-199937030-00003
Chi KN, Spratlin J, Kollmannsberger C, North C, Pankras C, Chien C, Gonzalez M, Peng L, Yu MK, Tran NP (2013) Evaluation of continuous abiraterone acetate (AA) plus prednisone (P) dosing in fasting and fed states in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) European Journal of Cancer 49 (http://eccamsterdam2013.ecco-org.eu/Scientific-Programme/Abstract-search.aspx?abstractid=6411)
Kim K, Johnson JA, Derendorf H (2004) Differences in drug pharmacokinetics between East Asians and Caucasians and the role of genetic polymorphisms. J Clin Pharmacol 44(10):1083–1105. doi:10.1177/0091270004268128
Bernard A, Vaccaro N, Acharya M et al (2014) Impact on abiraterone pharmacokinetics and safety: open-label drug–drug interaction studies with ketoconazole and rifampicin. Clin Pharmacol Drug Dev. doi:10.1002/cpdd.132
Lamba JK, Lin YS, Schuetz EG, Thummel KE (2002) Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 54(10):1271–1294
Jada SR, Xiang X, Zhou Q, Li HH, Ooi LL, Chowbay B (2006) Hepatic expression of CYP3A4 and CYP3A5 genes in Asians and implications for pharmacokinetic variations during chemotherapy Journal of Clinical Oncolog, ASCO Annual Meeting Proceedings 24, 18S
Ingelman-Sundberg M (2004) Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn Schmiedebergs Arch Pharmacol 369(1):89–104
Hildebrandt MA, Carrington DP, Thomae BA, Eckloff BW, Schaid DJ, Yee VC, Weinshilboum RM, Wieben ED (2007) Genetic diversity and function in the human cytosolic sulfotransferases. Pharmacogenomics J 7(2):133–143. doi:10.1038/sj.tpj.6500404
Acknowledgments
We acknowledge PRA International, the Netherlands, for analyzing all plasma samples for abiraterone. The authors are most grateful to the study subjects for their contributions and the investigational staff for the medical care. The authors acknowledge Ashwini Patil, MS (SIRO Clinpharm Pvt. Ltd.) for writing assistance (funded by Janssen Research and Development, LLC), and Namit Ghildyal, PhD (Janssen Research & Development, LLC) for additional editorial support for the development of this manuscript. The authors received funding support from Janssen Research and Development Division, NV, Belgium, Janssen Pharmaceutical, KK, Japan, and Janssen Research & Development, LLC, USA.
Conflict of interest
All authors are employees of Johnson & Johnson. Dr. Chien, Dr. Yu, Mr. Shishido, Ms. Bernard, Ms. Vaccaro, and Mr. Stieltjes own stock options in the company.
Author information
Authors and Affiliations
Corresponding author
Additional information
The study PCR 1005 is registered at ClinicalTrials. gov: NCT01575587.
Rights and permissions
About this article
Cite this article
Inoue, K., Shishido, A., Vaccaro, N. et al. Pharmacokinetics of abiraterone in healthy Japanese men: dose-proportionality and effect of food timing. Cancer Chemother Pharmacol 75, 49–58 (2015). https://doi.org/10.1007/s00280-014-2616-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-014-2616-4