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Intravitreal Pharmacokinetics and Retinal Concentrations of Ganciclovir and Foscarnet after Intravitreal Administration in Rabbits

¹ From the Infectious Diseases Service and the ² Department of Ophthalmology, Hospital Universitario Virgen del Rocío, Seville; and ³ Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Seville, Spain.

PURPOSE. To perform a detailed pharmacokinetic study and to evaluate the drug levels reached in the retina after the intravitreal administration of ganciclovir and foscarnet to rabbits.

METHODS. Retinal and vitreal levels of both drugs were measured by high-performance liquid chromatography at 1, 6, 12, 24, 36, 48, 60, and 72 hours after a single intravitreal injection of 196 µg and 800 µg of ganciclovir and 960 µg of foscarnet to three groups of 24 pigmented rabbits. A noncompartmental pharmacokinetic analysis was used.

RESULTS. Both drugs incorporated rapidly into the retina, but no equilibrium was observed between the drug levels in the vitreous humor and retina. Mean ganciclovir levels in vitreous and retina were 179.6 µg/g and 131.3 µg/g (dose of 196 µg), 755.7 µg/g and 381.6 µg/g (dose of 800 µg) at 1 hour after administration, decreasing to 0.1 µg/g, 0.6 µg/g, 0.8 µg/g, and 0.7 µg/g, respectively, by 72 hours. Mean foscarnet levels in vitreous and retina were 944 µg/g and 217.1 µg/g at 1 hour after administration, decreasing to 74 µg/g and 17.1 µg/g, respectively, by 72 hours. Whereas both doses of ganciclovir yielded retinal levels above the mean inhibitory concentration (IC₅₀) of most human cytomegalovirus (CMV) isolates for more than 60 hours, foscarnet retinal levels were lower than the CMV IC₅₀ before 36 hours had elapsed after administration.

CONCLUSIONS. The results suggest that the intravitreal administration of ganciclovir has a better pharmacokinetic profile than foscarnet for the treatment of retinitis caused by CMV and other herpes viruses and support the administration of intravitreal ganciclovir twice a week as a treatment for CMV retinitis.