Pharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer.
AuthorsRanson, Malcolm R
Wilson, R H
O'Sullivan, J M
Cowan, Richard A
Logue, John P
AffiliationDepartment of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester, Center for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK, Chiba Cancer Center, Chiba, Harasanshin Hospital, Fukuoka, Japan, AstraZeneca, Alderley Park, Macclesfield, UK, AstraZeneca KK, and Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
MetadataShow full item record
AbstractObjective: To investigate potential differences in zibotentan pharmacokinetics between Japanese and Caucasian patients with hormone-resistant prostate cancer (HRPC) following single and multiple dosing. Methods: In the Japanese study, 18 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 26 days' once-daily dosing. In the Caucasian study, 21 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 12 days' once-daily dosing. Results: Pharmacokinetic parameters were similar between populations. Absorption of zibotentan was rapid with maximum plasma concentrations typically achieved within 3 h of dosing. Mean clearance, 17.9 and 18.7 ml/min in Japanese and Caucasian patients, respectively (range 7.0 - 36.3 ml/min in Japanese patients and 7.8 - 29.5 ml/min in Caucasian patients) and volume of distribution, 14.0 and 15.6 l for Japanese and Caucasian patients, respectively (range 7.9 - 29.1 l in Japanese patients and 9.6 - 23.8 l in Caucasian patients) were relatively low, and t1/2 was approximately 12 h (range 5.7 - 18.8 h in Japanese patients and 5.0 - 22.9 h in Caucasian patients) following single dosing. Little accumulation was observed following daily dosing and multiple-dose pharmacokinetics were predictable. Exposure levels achieved in some Japanese patients receiving zibotentan 15 mg were higher than those observed in Caucasian patients, however, this may be due to differences in body weight, as exposure levels were similar when data were normalized for body weight. Zibotentan was well tolerated in both populations. Conclusions: There are no clinically relevant differences in the disposition and pharmacokinetics of zibotentan between Japanese and Caucasian patients with HRPC.
CitationPharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer. 2010, 48 (11):708-17 Int J Clin Pharmacol Ther
JournalInternational Journal of Clinical Pharmacology and Therapeutics
- Single- and multiple-dose pharmacokinetics, safety and tolerability of zibotentan (ZD4054) in Chinese men with advanced solid tumors.
- Authors: Li J, Liu Y, Qian J, Wu L, Kemp J, Nii M, Tomkinson H, Zuo Y, Ranson M, Usami M
- Issue date: 2012 Jul
- Preliminary study of the specific endothelin a receptor antagonist zibotentan in combination with docetaxel in patients with metastatic castration-resistant prostate cancer.
- Authors: Trump DL, Payne H, Miller K, de Bono JS, Stephenson J 3rd, Burris HA 3rd, Nathan F, Taboada M, Morris T, Hubner A
- Issue date: 2011 Sep
- A phase I study of zibotentan (ZD4054) in patients with metastatic, castrate-resistant prostate cancer.
- Authors: Schelman WR, Liu G, Wilding G, Morris T, Phung D, Dreicer R
- Issue date: 2011 Feb
- Health-related quality of life in pain-free or mildly symptomatic patients with metastatic hormone-resistant prostate cancer following treatment with the specific endothelin A receptor antagonist zibotentan (ZD4054).
- Authors: Dawson N, Payne H, Battersby C, Taboada M, James N
- Issue date: 2011 Jan
- Disposition and metabolism of the specific endothelin A receptor antagonist zibotentan (ZD4054) in healthy volunteers.
- Authors: Clarkson-Jones JA, Kenyon AS, Kemp J, Lenz EM, Oliver SD, Swaisland H
- Issue date: 2012 Apr