Abstract
Background: A drug and disease assessment model was used to evaluate the impact of different treatment regimens on intravitreal ranibizumab, bevacizumab, aflibercept, and brolucizumab concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF. Methods: A time-dependent mathematical model using Wolfram Mathematica software was used. The pharmacokinetic and pharmacodynamic data for anti-VEGFs were obtained from published reports. The model simulated drug concentration after single and multiple doses of ranibizumab, bevacizumab, aflibercept, and brolucizumab, and it extrapolated time-dependent intraocular free VEGF proportion values. Various fixed treatment regimens (q4, q8, q10, q12) were simulated and evaluated as candidates for clinical utilization. Results: Our mathematical model shows good correlation between intraocular VEGF proportion values and clinical data. Simulations suggest that each anti-VEGF agent would allow for distinct treatment intervals to keep the proportion of free VEGF under threshold levels. Regimens scheduling q8 ranibizumab, q8 bevacizumab, q12 aflibercept, and q10 brolucizumab administration permit to maintain the proportion of unbound VEGF below 0.001%. Conclusions: Fixed q8 ranibizumab, q8 bevacizumab, q12 aflibercept, or q10 brolucizumab regimens may produce adequate intraocular VEGF inhibition.
Highlights
The development and widespread use of intravitreal endothelial growth factor (VEGF)inhibitors has transformed the management of neovascular age-related macular degeneration (AMD), reducing the number of cases of legal blindness by 50% over the last decade [1,2]
The research methodology was focused on the combination of medical subject headings and the keywords: “age-related macular degeneration”, “choroidal neovascularization”, “anti-vascular endothelial growth factor (VEGF)”, “AMD”, “CNV”, “aflibercept”, “bevacizumab”, “ranibizumab”, and “brolucizumab”
Ranibizumab was approved by the United States Food and Drug Administration for treating neovascular AMD in 2006 as a consequence of the results of phase III MARINA
Summary
The development and widespread use of intravitreal endothelial growth factor (VEGF)inhibitors has transformed the management of neovascular age-related macular degeneration (AMD), reducing the number of cases of legal blindness by 50% over the last decade [1,2]. San Francisco, CA, USA and Novartis Pharma AG, Basel, Switzerland), and bevacizumab A considerable amount of data have been accumulated regarding the pharmacokinetic characteristics of anti-VEGF drugs that may guide dosing frequency and optimize clinical efficacy [5,6,7,8,9,10]. According to their intraocular pharmacokinetic properties, these drugs have relatively short half-lives, thereby requiring frequent injections to maintain their efficacy. To mitigate the treatment burden associated with intravitreal dosing of anti-VEGF drugs, research has focused on identifying agents with
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.