LIPOSOMALLY-ENTRAPPED GANCICLOVIR FOR THE TREATMENT OF CYTOMEGALOVIRUS RETINITIS IN AIDS PATIENTS - EXPERIMENTAL TOXICITY AND PHARMACOKINETICS, AND CLINICAL-TRIAL

Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requi res frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intr avitreal application of liposomally-entrapped GCV could prolong intrao cular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single i ntravitreal injection of either different doses of the free drug (0.2- 20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitr eous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected aft er 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals inje cted with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed n o retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 +/- 0.39 mug/ ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remissio n of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2-4 mon th follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatme nt of CMV retinitis.