Singapore Drugs Database

Indication

Treatment of advanced renal cell cancer and advanced soft tissue sarcoma (in patients previously treated with chemotherapy)

Mechanism of Action

Pazopanib is a second-generation multitargeted tyrosine kinase inhibitor against vascular endothelial growth factor receptor-1, -2, and -3, platelet-derived growth factor receptor-alpha, platelet-derived growth factor receptor-beta, and c-kit. These receptor targets are part of the angiogenesis pathway that facilitates the formation of tumour blood vessel for tumour survival and growth.

Pharmacokinetics

Absorption

Absorption of pazopanib in cancer patients is slow and incomplete. In patients with solid tumour, over a dose range of 50-2000 mg, absorption is nonlinear. Significant accumulation of pazopanib can also be observed in patients receiving 800 mg once daily for 22 days. Crushing tablets may increase exposure (increase in Cmax and AUC, while Tmax decreases by 2 hours). Bioavailability, oral tablet 800 mg, cancer patient = 21%; Bioavailability may be low due to incomplete absorption from the gastrointestinal tract. The major circulating component of the drug in the systemic is pazopanib, and not its metabolites. Mean maximum plasma concentration= 58.1 µg/mL; Mean AUC= 1037 µg · h/mL;

Distribution

Vd steady state, IV administration 5 mg, cancer patient = 11.1 L (range of 9.15 - 13.4)

Metabolism

Metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C8. Metabolites are less active than pazopanib (10 to 20-fold less active). Three of its metabolites can be observed in the systemic and account for

Elimination

Clearance

CL, cancer patient, IV administration 5 mg = 4mL/min Half of the absorbed dose is cleared via oxidative metabolism.

Active Ingredient/Synonyms

GW 78603 | Pazopanibum | Pazopanib |