A physiologically based pharmacokinetic model for the intraocular distribution of pilocarpine in rabbits

This report presents a mathematical model which has been developed to describe the intraocular disposition of pilocarpine following topical dosing in rabbits. The model uses experimentally determined parameters such as rates of tissue uptake of drug and equilibrium distribution coefficients. Differential mass balance equations for pilocarpine in the cornea, aqueous humor, iris-ciliary body, and lens were written and solved numerically. Measured tear concentrations, following topical dosing wih pilocarpine, were fit by a monoexponential curve and used as the forcing function of the model. By using a combination of known physiological and experimentally determined parameters, predictions of intraocular tissue levels of pilocarpine were made. These predictions were then compared to experimentally determined concentration-time profiles.