Abstract
AbstractAge-related macular degeneration (AMD) is a condition brought on by macular deterioration caused primarily by inflammation and cell death in the retina. There is no cure for the disease and current treatments for advanced (wet) AMD rely on intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) therapeutics. One common off-label anti-VEGF drug used in AMD treatment is bevacizumab. There have been experimental efforts to investigate the pharmacokinetic (PK) behavior of bevacizumab in the vitreous and aqueous humor. Still the quantitative effect of elimination routes and drug concentration in the macula are not well understood. In our study, we developed two spatial models representing rabbit and human vitreous humor to better understand the PK behavior of bevacizumab. We explored convective effects on the vitreous while considering the anterior elimination alone or coupled with posterior elimination. We compared our models with available experimental data and calculated an approximate macula concentration. Our results show that both anterior and posterior elimination play a role in bevacizumab clearance from the eye. Furthermore, an effective bevacizumab concentration close to the macula region is maintained for shorter time periods when compared to the whole vitreous region. This model can improve knowledge and understanding of AMD treatment.
Publisher
Cold Spring Harbor Laboratory