Clinical Pharmacokinetics and Pharmacodynamics of Pazopanib: Towards Optimized Dosing.

ABSTRACT: Pazopanib is an inhibitor of the vascular endothelial growth factor receptor, platelet-derived growth factor receptor, fibroblast growth factor receptor and stem cell receptor c-Kit, and has been approved for the treatment of renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib are complex and are characterized by pH-dependent solubility, large interpatient variability and low, non-linear and time-dependent bioavailability. Exposure to pazopanib is increased by both food and coadministration of ketoconazole, but drastically reduced by proton pump inhibitors. Studies have demonstrated relationships between systemic exposure to pazopanib and toxicity, such as hypertension. Furthermore, a strong relationship between pazopanib trough level ≥20 mg/L and both tumor shr

SUBMITTER: Verheijen RB 

PROVIDER: S-EPMC5563343 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature