Pharmacokinetics of sunitinib malate in subjects with hepatic impairment.

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 AUC(0-infinity) was 1,938, 2,002, and 1,999 ng h/ml, TD AUC(0-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.