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Pharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer.

Journal Article


Abstract


  • Objective

    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.

Publication Date


  • 2010

Citation


  • Ranson, M., Wilson, R. H., O'Sullivan, J. M., Maruoka, M., Yamaguchi, A., Cowan, R. A., . . . Usami, M. (2010). Pharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer.. International journal of clinical pharmacology and therapeutics, 48(11), 708-717. doi:10.5414/cpp48708

Web Of Science Accession Number


Start Page


  • 708

End Page


  • 717

Volume


  • 48

Issue


  • 11

Place Of Publication


Abstract


  • Objective

    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.

Publication Date


  • 2010

Citation


  • Ranson, M., Wilson, R. H., O'Sullivan, J. M., Maruoka, M., Yamaguchi, A., Cowan, R. A., . . . Usami, M. (2010). Pharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer.. International journal of clinical pharmacology and therapeutics, 48(11), 708-717. doi:10.5414/cpp48708

Web Of Science Accession Number


Start Page


  • 708

End Page


  • 717

Volume


  • 48

Issue


  • 11

Place Of Publication