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Axitinib plasma pharmacokinetics and ethnic differences

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Summary

Axitinib, a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, showed improved progression-free survival over sorafenib in patients previously treated for advanced renal cell carcinoma in the AXIS trial. Although a few studies had established the efficacy and safety of axitinib in Asian patients, additional evaluation was necessary to obtain regulatory approval in several Asian countries, especially in light of ethnic differences that are known to exist in genetic polymorphisms for metabolizing enzymes such as cytochrome P450 (CYP) 3A5, CYP2C19 and uridine diphosphate glucuronosyltransferase (UGT) 1A1, which are involved in axitinib metabolism. Axitinib plasma pharmacokinetics following single or multiple administration of oral axitinib in Asian (Japanese or Chinese) healthy subjects as well as Asian patients with advanced solid tumors was compared with that obtained in Caucasians. Upon review, the data demonstrated that axitinib can be characterized as not sensitive to ethnic factors based on its pharmacokinetic and pharmacodynamic properties. Axitinib exhibited similar pharmacokinetics in Asian and non-Asian subjects. A pooled population pharmacokinetic analysis indicated lack of a clinically meaningful effect of ethnicity on axitinib disposition. Therefore, dose adjustment for axitinib on the basis of ethnicity is not currently warranted.

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Acknowledgments

The development of this review manuscript was funded by Pfizer Inc. Writing support was provided by Mariko Nagashima, PhD (Engage Scientific Solutions, Southport, CT, USA), and funded by Pfizer Inc.

Disclosure statements

Ying Chen, May Garrett, Robert R. LaBadie and Yazdi K. Pithavala are employees of and own stock in Pfizer Inc. Akiyuki Suzuki and Yoshiko Umeyama are employees of Pfizer Japan Inc and own stock in Pfizer Inc. Michael A Tortorici, was employed by Pfizer Inc at the initiation of development of this review and owns stock in Pfizer Inc, and is currently an employee of CSL Behring Biotherapies for Life (King of Prussia, PA, USA).

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Authors and Affiliations

  1. Clinical Pharmacology, Pfizer Inc, 10555 Science Center Drive, San Diego, CA, 92121, USA

    Ying Chen, May Garrett & Yazdi K. Pithavala

  2. Pfizer Japan Inc, 3-22-7, Yoyogi, Shibuya-ku, Tokyo, 1518589, Japan

    Akiyuki Suzuki & Yoshiko Umeyama

  3. Clinical Pharmacology and Pharmacometrics, CSL Behring Biotherapies for Life, 1020 First Avenue, King of Prussia, PA, 19406, USA

    Michael A. Tortorici

  4. Pfizer Inc, 558 Eastern Point Road, Groton, CT, 06340, USA

    Robert R. LaBadie

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  1. Ying Chen
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Correspondence to Yazdi K. Pithavala.

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Michael A. Tortorici was employed by Pfizer Inc at the time of studies presented in this review.

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Chen, Y., Suzuki, A., Tortorici, M.A. et al. Axitinib plasma pharmacokinetics and ethnic differences. Invest New Drugs 33, 521–532 (2015). https://doi.org/10.1007/s10637-015-0214-x

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