Ocular disposition of novel lipophilic diester prodrugs of ganciclovir following intravitreal administration using microdialysis

Purpose. The objective of the present study was to explore acyl diester prodrugs (acetate, propionate, and butyrate) of ganciclovir (GCV) to achieve sustained therapeutic concentrations of GCV in the vitreous over a prolonged period of time following intravitreal administration. Methods. Male New Zealand albino rabbits (2–2.5 kg) were used for these studies. Animals were kept under anesthesia throughout the course of an experiment using ketamine HCl and xylazine. A concentric microdialysis probe was implanted into the vitreous chamber with a 21-gauge needle and a linear microdialysis probe was inserted into the anterior chamber across the cornea using a 25-gauge needle. The probes were perfused with isotonic phosphate buffer saline (pH 7.4) at a flow rate of 2µl/min. GCV prodrugs (33.2µg of diacetate, 35.9µg dipropionate prodrugs, and 9.87µg of dibutyrate prodrug) or GCV (50, 25, and 12.5µg) were administered intravitreally and the microdialysis samples were collected every 20 minutes over a period of 10 ...