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Eva María del Amo Páez, Arto Urtti; Computational Prediction of Intravitreal Pharmacokinetics of Macromolecules: Tool for Ocular Drug Development. Invest. Ophthalmol. Vis. Sci. 2016;57(12):291. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Intravitreal pharmacokinetics is important in the development of ocular medications, but computational tools for intravitreal pharmacokinetic prediction are missing. We aimed to develop pharmacokinetic simulation models to predict the intravitreal concentrations of biologicals after intravitreal administration. Such models are needed in ocular drug development to estimate the drug doses during chronic treatments with injections or long acting drug delivery systems.
The primary pharmacokinetic parameter values of a universal collection of intravitreal macromolecule drugs (7.1-149 kDa) in rabbit eye were used: 80% of the molecules presented intravitreal volume of distribution of 1.2-2.3 ml and clearance from the vitreous of 0.011 – 0.025 ml/h. The values were implemented into pharmacokinetic simulation models for drugs in solution or in controlled delivery systems using STELLA® Modelling & Simulation software.
The pharmacokinetic simulation models with macromolecules yielded good estimates of vitreous drug concentrations. The models could be used for dosage form design to estimate the required release rates and doses that are needed to reach the target concentration profile. The translation from intravitreal rabbit data into intravitreal human prediction is possible.
The present work offers useful in silico predictions of vitreal concentration profiles of macromolecule drugs after intravitreal injection, either in solution or incorporated in implants. Such in silico models are expected to advance ocular drug development.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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