ArticleBritish journal of clinical pharmacology2011
A mechanism-based model for the population pharmacokinetics of free and bound aflibercept in healthy subjects.
Article in British journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Comparison of the efficacy and safety of SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration.Scientific reports · 2024Trial
- Systemic exposure to aflibercept after intravitreal injection in premature neonates with retinopathy of prematurity: results from the FIREFLEYE randomized phase 3 study.Eye (London, England) · 2024Trial
- Calculating Receptor Occupancy using TMDD Models - What has to be Considered?The AAPS journal · 2026Article
- Integrated Population Pharmacokinetic Analysis of Intravitreal Aflibercept Drug Products.CPT: pharmacometrics & systems pharmacology · 2026Article
- Treatment of Exudative Age-related Macular Degeneration: Focus on Aflibercept.Drugs & aging · 2015Review
- A Tutorial on Target-Mediated Drug Disposition (TMDD) Models.CPT: pharmacometrics & systems pharmacology · 2015Article
- Vascular endothelial growth factor trap-eye and trap technology: Aflibercept from bench to bedside.Oman journal of ophthalmology · 2014Review
- What is the evidence for systemic effects of intravitreal anti-VEGF agents, and should we be concerned?The British journal of ophthalmology · 2014Review
- Mechanistic pharmacokinetic/target engagement/pharmacodynamic (PK/TE/PD) modeling in deciphering interplay between a monoclonal antibody and its soluble target in cynomolgus monkeys.The AAPS journal · 2014Article
- Vascular endothelial growth factor trap-eye (Aflibercept) for the management of diabetic macular edema.World journal of diabetes · 2013Review
- Development of a preclinical PK/PD model to assess antitumor response of a sequential aflibercept and doxorubicin-dosing strategy in acute myeloid leukemia.The AAPS journal · 2013Article
- Aflibercept: a Potent Vascular Endothelial Growth Factor Antagonist for Neovascular Age-Related Macular Degeneration and Other Retinal Vascular Diseases.Biologics in therapy · 2012Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimAflibercept (VEGF-Trap), a novel anti-angiogenic agent that binds to VEGF, has been investigated for the treatment of cancer. The aim of this study was to develop a mechanism-based pharmacokinetic (PK) model for aflibercept to characterize its binding to VEGF and its PK properties in healthy subjects.
methodsData from two phase I clinical studies with aflibercept administered as a single intravenous infusion were included in the analysis. Free and bound aflibercept concentration-time data were analysed using a nonlinear mixed-effects modelling approach with MONOLIX 3.1.
resultsThe best structural model involved two compartments for free aflibercept and one for bound aflibercept, with a Michaelis-Menten type binding of free aflibercept to VEGF from the peripheral compartment. The typical estimated clearances for free and bound aflibercept were 0.88 l day(-1) and 0.14 l day(-1), respectively. The central volume of distribution of free aflibercept was 4.94 l. The maximum binding capacity was 0.99 mg day(-1) and the concentration of aflibercept corresponding to half of maximum binding capacity was 2.91 µg ml(-1). Interindividual variability of model parameters was moderate, ranging from 13.6% (V(max) ) to 49.8% (Q).
conclusionThe present PK model for aflibercept adequately characterizes the underlying mechanism of disposition of aflibercept and its nonlinear binding to VEGF.
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