Chem. Pharm. Bull. 58(10): 1301-1305 (2010)

It is well known that ocular bioavailability after topical instillation is extremely low compared with the other administration including oral administration, transdermal application, vitreous injection, and implantable delivery. The ocular bioavailability is also affected by a variety of pharmaceutical factors such as formulation viscosity and the particle size of suspension, and so on. In spite of the fact that the elimination of the drugs from the eye is influenced by the pathological conditions of the barrier membranes such as the retina/choroid/sclera (RCS) membrane and cornea, little is known with respect to the effect of pathological conditions on the ocular pharmacokinetics. Drugs are usually administered under diseased conditions that may differ from those present normally. It is therefore difficult to predict drug movement in the eye under diseased conditions with conventional compartment models assuming uniform concentrations in each ocular tissue. In the present study, we have developed the pharmacokinetic model for ocular drug delivery on the basis of the diffusion model. The concentration profiles after topical instillation calculated were compared with the in vivo rabbit experimental data reported in the literature. In addition, we have examined drug movement in the eye with pathology by assuming a barrier capacity of the surrounding membranes decreased under pathological conditions.