Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose
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. Metho...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1416 |
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| author | Daniele Veritti Valentina Sarao Francesco Di Bin Paolo Lanzetta |
| author_facet | Daniele Veritti Valentina Sarao Francesco Di Bin Paolo Lanzetta |
| author_sort | Daniele Veritti |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T03:24:25Z |
| format | Article |
| id | doaj.art-6cd4aafe85124790b97491d84510406f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:25Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6cd4aafe85124790b97491d84510406f2023-11-18T02:51:16ZengMDPI AGPharmaceutics1999-49232023-05-01155141610.3390/pharmaceutics15051416Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept DoseDaniele Veritti0Valentina Sarao1Francesco Di Bin2Paolo Lanzetta3Department of Medicine–Ophthalmology, University of Udine, 33100 Udine, ItalyDepartment of Medicine–Ophthalmology, University of Udine, 33100 Udine, ItalyDepartment of Medicine–Ophthalmology, University of Udine, 33100 Udine, ItalyDepartment of Medicine–Ophthalmology, University of Udine, 33100 Udine, ItalyBackground: 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.https://www.mdpi.com/1999-4923/15/5/1416age-related macular degenerationafliberceptburdenintravitreal injectionsmathematical modelneovascular |
| spellingShingle | Daniele Veritti Valentina Sarao Francesco Di Bin Paolo Lanzetta Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose Pharmaceutics age-related macular degeneration aflibercept burden intravitreal injections mathematical model neovascular |
| title | Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose |
| title_full | Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose |
| title_fullStr | Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose |
| title_full_unstemmed | Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose |
| title_short | Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose |
| title_sort | pharmacokinetic and pharmacodynamic rationale for extending vegf inhibition increasing intravitreal aflibercept dose |
| topic | age-related macular degeneration aflibercept burden intravitreal injections mathematical model neovascular |
| url | https://www.mdpi.com/1999-4923/15/5/1416 |
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