Background: The effects of various dosages and treatment regimens on intravitreal aflibercept concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF were evaluated using a drug and disease assessment model. The 8 mg dosage received specific attention. Methods: A time-dependent mathematical model was developed and implemented using Wolfram Mathematica software v12.0. This model was used to obtain drug concentrations after multiple doses of different aflibercept dosages (0.5 mg, 2 mg, and 8 mg) and to estimate the time-dependent intravitreal free VEGF percentage levels. A series of fixed treatment regimens were modeled and evaluated as potential clinical applications. Results: The simulation results indicate that 8 mg aflibercept administered at a range of treatment intervals (between 12 and 15 weeks) would allow for the proportion of free VEGF to remain below threshold levels. Our analysis indicates that these protocols maintain the ratio of free VEGF below 0.001%. Conclusions: Fixed q12-q15 (every 12-15 weeks) 8 mg aflibercept regimens can produce adequate intravitreal VEGF inhibition.

Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose

Veritti, Daniele
;
Di Bin, Francesco;Lanzetta, Paolo
2023-01-01

Abstract

Background: The effects of various dosages and treatment regimens on intravitreal aflibercept concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF were evaluated using a drug and disease assessment model. The 8 mg dosage received specific attention. Methods: A time-dependent mathematical model was developed and implemented using Wolfram Mathematica software v12.0. This model was used to obtain drug concentrations after multiple doses of different aflibercept dosages (0.5 mg, 2 mg, and 8 mg) and to estimate the time-dependent intravitreal free VEGF percentage levels. A series of fixed treatment regimens were modeled and evaluated as potential clinical applications. Results: The simulation results indicate that 8 mg aflibercept administered at a range of treatment intervals (between 12 and 15 weeks) would allow for the proportion of free VEGF to remain below threshold levels. Our analysis indicates that these protocols maintain the ratio of free VEGF below 0.001%. Conclusions: Fixed q12-q15 (every 12-15 weeks) 8 mg aflibercept regimens can produce adequate intravitreal VEGF inhibition.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11390/1249865
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