Prediction of the Vitreal Half-Life of Small Molecular Drug-Like Compounds

Abstract

To build a fast, user-friendly computational model to predict the intravitreal half-lives of drug-like compounds. We used multivariate analysis to build intravitreal half-life models using two data sets, one with experimental data derived from both pigmented and albino rabbits and another including only data from experiments with albino rabbits. The final models had a Q(2) value of 0.65 and 0.75 for the mixed and albino rabbit models, respectively. The models performed well in predicting the intravitreal half-life of an external test set. In addition, the models are physiologically interpretable, containing mainly hydrogen bonding and lipophilicity descriptors. The developed models enable reliable predictions of intravitreal half-lives for use in the early drug development stages, without the need for prior experimental data.