Intravitreal pharmacokinetics and retinal concentrations of ganciclovir and foscarnet after intravitreal administration in rabbits

PURPOSE. To perform a detailed pharmacokinetic study and to evaluate the dr ug levels reached in the retina after the intravitreal administration of ga nciclovir and foscarnet to rabbits. METHODS. Retinal and vitreal levels of both drugs were measured by high-per formance liquid chromatography at 1, 6, 12, 24, 36, 48. 60, and 72 hours af ter a single intravitreal injection of 190 mug and 800 mug of ganciclovir a nd 960 mug of foscarnet to three groups of 24 pigmented rabbits. A noncompa rtmental pharmacokinetic analysis was used. RESULTS. Both drugs incorporated rapidly into the retina, but no equilibriu m was observed between the drug levels in the vitreous hurmor and retina. M ean ganciclovir levels in vitreous and retina were 179.6 mug/g and 131.3 mu g/g (dose of 196 mug), 755.7 mug/g and 381.6 mug/g (dose of 800 mu8) at 1 h our after administration, decreasing to 0.1 mug/g, 0.6 mug/g, 0.8 mug/g, an d 0.7 mug/g, respectively, by 72 hours. Mean foscarnet levels in vitreous a nd retina were 944 mug/g and 217.1 mug/g at 1 hour after administration, de creasing to 74 mug/g and 17,1 mug/g, respectively, by 72 hours. Whereas bot h doses of ganciclovir yielded retinal levels above the mean inhibitory con centration (IC50) of most human cytomegalovirus (CMV) isolates for more tha n 60 hours, foscarnet retinal levels were lower than the CMV IC50, before 3 6 hours had elapsed after administration. CONCLUSIONS. The results suggest that the intravitreal administration of ga nciclovir has a better pharmacokinetic profile than foscarnet for the treat ment of retinitis caused by CMV and other herpes viruses and support the ad ministration of intravitreal ganciclovir twice a week as a treatment for CM V retinitis.