Single- and multiple-dose disposition kinetics of sunitinib malate, a multitargeted receptor tyrosine kinase inhibitor: comparative plasma kinetics in non-clinical species

Cancer Chemother Pharmacol. 2009 Sep;64(4):691-706. doi: 10.1007/s00280-008-0917-1. Epub 2009 Jan 25.


Purpose: The purpose of these extensive non-clinical studies was to assess pharmacokinetics and dispositional properties of sunitinib and its primary active metabolite (SU12662).

Methods: Sunitinib was administered in single and repeat oral doses in mice, rats, and monkeys. Assessments were made using liquid-chromatography-tandem mass spectrometric methods, radioactive assays, and quantitative whole body autoradiography.

Results: Sunitinib was readily absorbed with good oral bioavailability and linear kinetics at clinically-relevant doses. SU12662 plasma levels were less than those of sunitinib in mice and monkeys, but greater in rats. Sunitinib was extensively distributed with moderate-to-high systemic clearance and eliminated primarily into feces. Single- and repeat-dosing kinetics were similar. A prolonged half-life allowed once-daily dosing, enabling adequate systemic exposure with limited-to-moderate accumulation. In multiple-dose studies with cyclic dosing, drug plasma concentrations cleared from one cycle to the next.

Conclusions: Sunitinib exhibited advantageous pharmacokinetic and dispositional properties in non-clinical species, translating into favorable properties in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Female
  • Indoles / administration & dosage
  • Indoles / blood
  • Indoles / pharmacokinetics*
  • Macaca fascicularis
  • Male
  • Mice
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / blood
  • Protein Kinase Inhibitors / pharmacokinetics*
  • Pyrroles / administration & dosage
  • Pyrroles / blood
  • Pyrroles / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Sunitinib
  • Tandem Mass Spectrometry


  • Antineoplastic Agents
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrroles
  • Receptor Protein-Tyrosine Kinases
  • Sunitinib