Abstract
Systemically circulating drugs may distribute to ocular tissues across the blood-ocular barriers. Ocular distribution is utilized in the treatment of ocular diseases with systemic medications, but ocular delivery of systemic drugs and xenobiotics may also lead to adverse ocular effects. Ocular distribution after systemic drug administration has not been predicted or modeled. In this study, distribution clearance between vitreous and plasma was obtained from a previous QSPR model for clearance of intravitreal drugs. These values were used in a pharmacokinetic simulation model to describe entry of unbound drug from plasma to vitreous. The simulation models predicted ocular distribution of 10 systemic drugs in rabbit eyes within 1.96 mean fold error and the distribution of cefepime from plasma to vitreous in humans. This is the first attempt to predict ocular distribution of systemic drugs. Reliable predictions were obtained using systemic concentrations of unbound drug, computational value of ocular distribution clearance, and a simple pharmacokinetic model. This approach can be used in drug discovery to estimate ocular drug exposure at an early stage.
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