Evaulation of Phamarcokinetics and Retinal Permeability for Ganciclovir in a Rabbit and Human Eye

Cytomegalovirus (CMV) is the most common cause of viral retinitis in patients with AIDS. Ganciclovir (GCV) has been widely used in the treatment of CMV retinitis. The GCV distribution in the vitreous is obviously influenced by the rate of elimination through the retina. The retinal permeability of GCV was calculated to be 9.25 x 10-5 cmls for both rabbit and human. The half-life of GCV in the vitreous was 6.8 hr and 13.2 hr for rabbit and human respectively. The difference of half-life between rabbit and human was only caused by the difference in the volume of vitreous humor. The numerical analyses provide a useful tool for identifying animal model and relevant parameter for developing drug delivery strategies to treat vitreoretinal diseases. INTRODUCTION Intravenous GCV is effective, but requires frequent and long-term intravenous dosing. Also, low permeability of the blood-retinal barrier may necessitate higher dosage during intravenous GCV administration to achieve therapeutic levels near the retina. The long term treatment and high dosage of GCV increases the risk of systemic adverse effects such as bone marrow suppression and neutropenia. To avoid the systemic adverse effect and overcome the blood-retinal barrier, intravitreal therapy such as intravitreal injection and controlled release implants are currently being used to treat CMV retinitis. The 50% effective dose (ED 50) of GCV for human CMV has a narrow concentration range (0.1-2.75 Ilg/ml). Therefore, to maximize the therapeutic benefits, it is critical to know GCV distribution within the eye following intravitreal administration. The GCV distribution in the vitreous is obviously influenced by the rate of elimination through the retina. In this study, retinal permeabilities and pharmacokinetics of GCVare evaluated in the rabbit and human eye. METHOD The model twelve-compartments of the eye are sclera, retinachoroid, vitreous, lens, posterior and anterior chamber, iris, Ciliary processes, hyaloid membrane, Schlemm's canal, cornea, and a drug' (2) Ophthalmology University of Cincinnati, Cincinnati,OH (4) Biomedical Engineering University of Cincinnati,