Axitinib in metastatic renal cell carcinoma: results of a pharmacokinetic and pharmacodynamic analysis.

ABSTRACT: Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved for second-line therapy for advanced renal cell carcinoma (RCC). Axitinib population pharmacokinetic and pharmacokinetic/pharmacodynamic relationships were evaluated. Using nonlinear mixed effects modeling with pooled data from 383 healthy volunteers, 181 patients with metastatic RCC, and 26 patients with other solid tumors in 17 trials, the disposition of axitinib was best described by a 2-compartment model with first-order absorption and a lag time, with estimated mean systemic clearance (CL) of 14.6 L/h and central volume of distribution (V(c)) of 47.3 L. Of 12 covariates tested, age over 60 years and Japanese ethnicity were associated with decreased CL, whereas V(c) increa

SUBMITTER: Rini BI 

PROVIDER: S-EPMC4175417 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature