Pharmacokinetic Simulations of Intravitreal Biologicals: Aspects of Drug Delivery to the Posterior and Anterior Segments.
Anna-Kaisa RimpeläIiro M A KiiskiFeng DengHeidi KidronArto UrttiPublished in: Pharmaceutics (2018)
Biologicals are important ocular drugs that are be delivered using monthly and bimonthly intravitreal injections to treat retinal diseases, such as age-related macular degeneration. Long acting delivery systems are needed for prolongation of their dosing interval. Intravitreal biologicals are eliminated from the eye via the aqueous humor outflow. Thus, the anterior and posterior segments are exposed to the drug. We utilized a kinetic simulation model to estimate protein drug concentrations in the vitreous and aqueous humor after bolus injection and controlled release administration to the vitreous. The simulations predicted accurately the experimental levels of 5 biologicals in the vitreous and aqueous humor. The good match between the simulations and experimental data demonstrated almost complete anterior segment bioavailability, and major dose sparing with ocular controlled release systems. Overall, the model is a useful tool in the design of intraocular delivery of biologicals.
Keyphrases
- age related macular degeneration
- diabetic retinopathy
- drug delivery
- molecular dynamics
- vascular endothelial growth factor
- ionic liquid
- monte carlo
- drug induced
- optic nerve
- optical coherence tomography
- ultrasound guided
- electronic health record
- amino acid
- emergency department
- machine learning
- cancer therapy
- adverse drug
- artificial intelligence
- small molecule
- big data
- platelet rich plasma
- deep learning
- endothelial cells
- drug release