Effect of food on the pharmacokinetics of sunitinib malate (SU11248), a multi-targeted receptor tyrosine kinase inhibitor: results from a phase I study in healthy subjects

The effect of food on the oral bioavailability of sunitinib malate (SU11248, an oral, multi-targeted tyrosine kinase inhibitor with anti-angiogenic and anti-tumor activities) was assessed in a randomized open-label, two-way crossover study. A 50-mg dose of SU11248 was administered to 16 healthy subjects after a 10-h fast in one period and after a high-fat, high-calorie meal in the other period. The 90% confidence intervals (Cls) for maximum plasma concentration (C-max) and area under the concentration-time curve (AUC) were within the 80-125% bioequivalence range, indicating the absence of a food effect. SU11248 exposure increased slightly in the fed compared with the fasted state (ratios of fed/fasted geometric least square means: C-max 104%, AUC(0-last) and AUC(0-infinity) both 112%). There was a delay in the formation/ absorption of the active metabolite SU12662 in the fed state (mean C-max decreased 23%), but exposure remained unaffected (90% Cls for AUC(0-last) and AUC(0-infinity) were within 80-125%). These results indicate that SU11248 can be administered with or without food.