Abstract
This study evaluated the effect of hepatic impairment on the pharmacokinetics of sunitinib and its active metabolite, SU12662. This open-label study enrolled subjects with normal hepatic function (n = 8), mild (Child–Pugh [CP]-A; n = 8), or moderate (CP-B; n = 8) hepatic impairment. Subjects received sunitinib 50 mg as a single oral dose. Mild or moderate hepatic impairment did not significantly alter sunitinib, SU12662, or total drug (TD) systemic exposure. In subjects with normal hepatic function, mild, or moderate hepatic impairment, respectively, TD AUC0–∞ was 1,938, 2,002, and 1,999 ng h/ml, TD AUC0–last was 1,913, 1,956, and 1,958 ng h/ml, and TD C max was 26.0, 27.3, and 26.7 ng/ml. There were no other notable pharmacokinetic differences and sunitinib was well tolerated. The pharmacokinetic findings of this study do not indicate a need to adjust the currently approved starting dose of sunitinib (50 mg daily on Schedule 4/2) for cancer patients with mild to moderate liver impairment.
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Acknowledgments
This study was supported by funding from Pfizer Inc. The authors would like to thank principal investigators Thomas Stock (Pfizer Clinical Research Unit, Ann Arbor, MI, USA) and Kenneth Lasseter (SFBC International, Miami, FL, USA), as well as study managers Rebecca Reynolds and Rhett Behrje. Editorial assistance was provided by ACUMED® (Tytherington, UK) with funding from Pfizer Inc.
Conflict of interest statement
The following authors have disclosures: C. L. Bello, M. Garrett, and J. Smeraglia are Pfizer employees. L. Sherman, B. Ryan, and M. Toh are former Pfizer employees. C. L. Bello, M. Garrett, M. Toh and L. Sherman own Pfizer shares.
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Laurie Sherman, Bob Ryan, and Melvin Toh are no longer Pfizer employees.
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Bello, C.L., Garrett, M., Sherman, L. et al. Pharmacokinetics of sunitinib malate in subjects with hepatic impairment. Cancer Chemother Pharmacol 66, 699–707 (2010). https://doi.org/10.1007/s00280-009-1213-4
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DOI: https://doi.org/10.1007/s00280-009-1213-4