(S-054) Computer Modeling of Bevacizumab Drug Distribution After Intravitreal Injection in Rabbit and Human Eyes

Eduardo Andres Chacin Ruiz – Chemical and Biological Engineering – University at Buffalo, The State University of New York; Jabia Chowdhury – Electrical Engineering – Texas A&M University-Texarkana; Ashlee Ford Versypt – Chemical and Biological Engineering – University at Buffalo, The State University of New York; Matthew Ohr – Ophthalmology and Visual Sciences – The Ohio State University; Katelyn Swindle-Reilly – Biomedical Engineering – The Ohio State University

Objectives: Wet age-related macular degeneration (AMD) is a chronic disease that can lead to central vision loss, primarily due to overexpression of vascular endothelial growth factor (VEGF). Bevacizumab, an anti-VEGF drug, is commonly administered off-label intravitreally once a month due to its short half-life in the vitreous. However, the quantitative effect of elimination routes and drug concentration in the macula are not well understood in the bevacizumab pharmacokinetic profile in the vitreous.

Methods: In a recently published work1, we developed two spatial computational models based on rabbit and human vitreous anatomy and physiology. The models were used to explore different drug elimination conditions and injection locations. Bevacizumab vitreous concentration and its half-life were calculated and compared to published data. Bevacizumab concentration in the macula was also estimated.

Results: Our 3D models successfully captured drug distribution in rabbit and human vitreous, in agreement with experimental data despite inter-individual variability. The model suggested that in rabbits, anterior elimination was the main route of drug clearance, whereas in humans, both anterior and posterior elimination contributed significantly to drug clearance. Furthermore, the modeling results showed that drug injection location does not substantially influence drug half-life or duration of action in the vitreous, but the peak concentration experienced at the fovea is affected.

Conclusions: The 3D models were able to successfully capture bevacizumab PK and provide insights into the relative contribution of elimination routes. Moreover, simulations can provide an estimate of bevacizumab drug concentration in the macula and help determine the duration of action of the drug. Such simulation results can be used to gain insight into different dosing regimens.

Citations: [1] J. M. Chowdhury, E. A. Chacin Ruiz, M. P. Ohr, K. E. Swindle-Reilly, A. N. Ford Versypt, Computer modeling of bevacizumab drug distribution after intravitreal injection in rabbit and human eyes, Journal of Pharmaceutical Sciences 114 (2) 1164–1174, 2025.

Keywords: Pharmacokinetics, Dynamic simulation, Mathematical model