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

Anticancer Drugs. 2006 Mar;17(3):353-8. doi: 10.1097/00001813-200603000-00015.

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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Biological Availability
  • Cross-Over Studies
  • Female
  • Food-Drug Interactions*
  • Humans
  • Indoles / adverse effects
  • Indoles / blood
  • Indoles / pharmacokinetics*
  • Male
  • Middle Aged
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Pyrroles / adverse effects
  • Pyrroles / blood
  • Pyrroles / pharmacokinetics*
  • Sunitinib

Substances

  • Indoles
  • Pyrroles
  • SU 12662
  • Protein-Tyrosine Kinases
  • Sunitinib