Posterior segment ocular pharmacokinetics using microdialysis in a conscious rabbit model

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Ocular Pharmacology
• Animal Models in Research

Background:

• Understanding ocular drug disposition is crucial for effective ophthalmic therapies.
• Previous studies often utilized anesthetized animal models, potentially confounding pharmacokinetic results.
• The impact of anesthesia and surgical procedures on ocular drug levels requires further investigation.

Purpose of the Study:

• To establish a conscious rabbit model for ocular pharmacokinetic investigations.
• To evaluate the influence of anesthesia and probe implantation on ganciclovir's ocular disposition.

Main Methods:

• Development of a conscious rabbit model for posterior ocular segment microdialysis.
• Comparison of three groups: no recovery/anesthetized, >5-day recovery/conscious, and >5-day recovery/anesthetized.
• Intravitreal administration of [3H] ganciclovir and determination of ocular levels over 10 hours using noncompartmental modeling.

Main Results:

• Microdialysis probes demonstrated functionality for at least 14 days.
• Anesthetized rabbits showed higher area under the curve (AUC) for ganciclovir compared to conscious rabbits.
• Vitreous half-life of ganciclovir was significantly shorter in conscious rabbits with a recovery period.

Conclusions:

• A reliable conscious rabbit model for ocular pharmacokinetics was successfully developed, usable for at least 14 days.
• Anesthesia enhances the ocular bioavailability of intravitreally administered ganciclovir.
• Probe implantation may increase protein efflux into the vitreous, potentially explaining altered ganciclovir half-life.