Ex vivo investigation of ocular tissue distribution following intravitreal administration of connexin43 mimetic peptide using the microdialysis technique and LC-MS/MS
PURPOSE To develop and establish a conscious rabbit model for ocular pharmacokinetic studies and to delineate the effects of anesthesia and probe implantation on the ocular disposition of ganciclovir. METHODS A conscious rabbit model was developed for microdialysis of the posterior ocular segment. Rabbits were divided into three groups. Group I consisted of rabbits with no recovery period after probe implantation and were anesthetized throughout the experiment. Group II consisted of rabbits that had a more than 5-day recovery period and were conscious during the experiment. Group III consisted of rabbits that had a more than 5-day recovery period and were anesthetized during the experiment. (3)[H] ganciclovir was administered (50 microL) intravitreously in all groups, and ocular levels were determined for 10 hours at appropriate time intervals. Data obtained were subjected to noncompartmental modeling. RESULTS Probe calibration studies indicated that the probes were functional for at least 14 days. The anesthetized groups, regardless of the period of recovery from probe implantation, exhibited higher areas under the curve than did the conscious group. The vitreous half-life of ganciclovir was significantly shorter in the groups with a recovery period of more than 5 days compared with the group with no recovery period. CONCLUSIONS The conscious rabbit model was developed and can be used for a period of at least 14 days. Anesthesia increased ocular bioavailability of intravitreously administered ganciclovir, whereas probe implantation led to increased protein efflux into the vitreous, which may be the reason for the increased half-life of ganciclovir in group I.