The Kinetics of Timolol in the Rabbit Lens: Implications for Ocular Drug Delivery

Abstract

This study examines the uptake and distribution of timolol in the rabbit lens following topical instillation using a heuristic approach. The implications of anisotropic drug diffusion through the lens are presented here and discussed in the context of actual in vivo data. The dynamics of timolol in the lens involve an initial, rapid uptake of the drug by the capsule and epithelium followed by slower, anisotropic diffusion through the cortex body. Kinetically, the capsule and epithelium can be treated as a separate compartment which is distinct from the cortex and which serves to provide a concentration gradient for subsequent diffusion of timolol into the dense interior structures of the lens. Model simulations support the hypothesis that the preferred route of penetration of timolol into the vitreous humor via the lens is the diffusion of drug around the capsule/epithelium and peripheral cortical layers. It is also shown that due to the high and increasing diffusional resistance toward the center of the lens, as well as the diminishing drug concentrations in the capsule and epithelium, steady-state levels in the lens may be extremely difficult to achieve in some therapeutic situations. This phenomenon could have a significant impact on the success or failure of a drug treatment involving the lens and ocular tissues.