ArticleBritish journal of clinical pharmacology2014
Population pharmacokinetic analysis of axitinib in healthy volunteers.
Article in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- A Systematic Evaluation of the Dosing Regimens for Approved Targeted Therapies and Immune Checkpoint Inhibitors in Metastatic Renal Cell Carcinoma From a Project OPTIMUS Perspective.Journal of clinical pharmacology · 2025Review
- Optimization of blood pressure measurement practices for pharmacodynamic analyses of tyrosine-kinase inhibitors.Clinical and translational science · 2023Article
- Absorption of the orally active multikinase inhibitor axitinib as a therapeutic index to guide dose titration in metastatic renal cell carcinoma.Investigational new drugs · 2021Article
- Model-Based Biomarker Selection for Dose Individualization of Tyrosine-Kinase Inhibitors.Frontiers in pharmacology · 2020Article
- The landscape of tyrosine kinase inhibitors in sarcomas: looking beyond pazopanib.Expert review of anticancer therapy · 2019Review
- Reviewing the role of healthy volunteer studies in drug development.Journal of translational medicine · 2018Review
- The FDA approved PI3K inhibitor GDC-0941 enhances in vitro the anti-neoplastic efficacy of Axitinib against c-myc-amplified high-risk medulloblastoma.Journal of cellular and molecular medicine · 2018Article
- The effect of medication nonadherence on progression-free survival among patients with renal cell carcinoma.Cancer management and research · 2017Article
- Drug-Drug Interaction Potentials of Tyrosine Kinase Inhibitors via Inhibition of UDP-Glucuronosyltransferases.Scientific reports · 2015Article
- Review
- Axitinib plasma pharmacokinetics and ethnic differences.Investigational new drugs · 2015Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAxitinib is a potent and selective second generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 approved for second line treatment of advanced renal cell carcinoma. The objectives of this analysis were to assess plasma pharmacokinetics and identify covariates that may explain variability in axitinib disposition following single dose administration in healthy volunteers.
methodsPlasma concentration-time data from 337 healthy volunteers in 10 phase I studies were analyzed, using non-linear mixed effects modelling (nonmem) to estimate population pharmacokinetic parameters and evaluate relationships between parameters and food, formulation, demographic factors, measures of renal and hepatic function and metabolic genotypes (UGT1A1*28 and CYP2C19).
resultsA two compartment structural model with first order absorption and lag time best described axitinib pharmacokinetics. Population estimates for systemic clearance (CL), central volume of distribution (Vc ), absorption rate constant (ka ) and absolute bioavailability (F) were 17.0 l h(-1) , 45.3 l, 0.523 h(-1) and 46.5%, respectively. With axitinib Form IV, ka and F increased in the fasted state by 207% and 33.8%, respectively. For Form XLI (marketed formulation), F was 15% lower compared with Form IV. CL was not significantly influenced by any of the covariates studied. Body weight significantly affected Vc , but the effect was within the estimated interindividual variability for Vc .
conclusionsThe analysis established a model that adequately characterizes axitinib pharmacokinetics in healthy volunteers. Vc was found to increase with body weight. However, no change in plasma exposures is expected with change in body weight; hence no dose adjustment is warranted.
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