title: 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.
abstract: 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 (CIs) for maximum plasma concentration (Cmax) 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: Cmax 104%, AUC0-last and AUC0-infinity both 112%). There was a delay in the formation/absorption of the active metabolite SU12662 in the fed state (mean Cmax decreased 23%), but exposure remained unaffected (90% CIs for AUC0-last and AUC0-infinity were within 80-125%). These results indicate that SU11248 can be administered with or without food.
authors.affiliation: Department of Clinical Pharmacology, Pfizer Global Research and Development, La Jolla, California 92121, USA.
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Bello
authors.forename: Laurie
authors.initials: L
authors.lastname: Sherman
authors.forename: Jihao
authors.initials: J
authors.lastname: Zhou
authors.forename: Lev
authors.initials: L
authors.lastname: Verkh
authors.forename: John
authors.initials: J
authors.lastname: Smeraglia
authors.forename: Janessa
authors.initials: J
authors.lastname: Mount
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Klamerus
mesh_terms: D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011758:Pyrroles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000077210:Sunitinib
chemical_list: D007211:Indoles; D011758:Pyrroles; C544393:SU 12662; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib