Pazopanib Hydrochloride

Pazopanib blocks several tyrosine kinases at once. These include vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, and fibroblast growth factor receptor (FGFR)-1 and -3. It also acts on the cytokine receptor (Kit), interleukin-2 receptor-inducible T-cell kinase (Itk), lymphocyte-specific protein tyrosine kinase (Lck), and the transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In vitro, it stopped ligand-induced autophosphorylation of the VEGFR-2, Kit and PDGFR-β receptors.

Absorption: Pazopanib is taken by mouth, and the median time to peak concentration is 2 to 4 hours after the dose. With daily dosing at 800 mg, the geometric mean AUC is 1,037 mcg/mL and the Cmax is 58.1 mcg/mL (equivalent to 132 µM). Going above 800 mg did not give a consistent rise in AUC or Cmax.

Distribution: In vivo, more than 99% of Pazopanib binds to human plasma protein, and this did not depend on concentration across the range of 10 to 100 mcg/mL. In vitro studies suggest Pazopanib is a substrate for P-gp and BCRP.

Metabolism: In vitro studies showed that CYP3A4 metabolizes Pazopanib, with a minor contribution from CYP1A2 and CYP2C8.

Elimination: After the recommended dose of 800 mg, the mean half-life of Pazopanib is 30.9 hours. Most of it leaves through the feces, and the kidneys account for less than 4% of the administered dose.