K D Rittenhouse1, R L Peiffer, G M Pollack. 1. Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
Abstract
PURPOSE: This study was conducted to assess the effects of anesthesia and aqueous humor protein concentrations on ocular disposition of propranolol. METHODS: Rabbits were anesthetized and a microdialysis probe was inserted into the anterior chamber of one eye; the contralateral eye served as a control. At timed intervals after probe placement, a 100-microl sample of aqueous humor was aspirated from each eye to determine protein concentration. In vitro protein binding parameters were used to simulate the impact of protein concentration on propranolol disposition. To assess the influence of anesthesia, probes were implanted in the anterior chamber of each eye. After >5-day stabilization, conscious and anesthetized rabbits (n = 3/group) received a 200-microg topical dose of [3H]DL-propranolol in each eye; propranolol was assayed in probe effluent. RESULTS: Changes in aqueous humor protein concentrations were observed following probe insertion. Simulations demonstrated that the unbound propranolol AUC (approximately 2.4-fold) in aqueous humor should be reduced due to protein influx. Intraocular propranolol exposure in anesthetized rabbits was approximately 8-fold higher than in conscious rabbits, and approximately 1.9-fold higher than in rabbits without a post-surgical recovery period. CONCLUSIONS: Anesthesia and time-dependent aqueous humor protein concentrations may alter ocular pharmacokinetics, and must be taken into account in the design of microdialysis experiments.
PURPOSE: This study was conducted to assess the effects of anesthesia and aqueous humor protein concentrations on ocular disposition of propranolol. METHODS:Rabbits were anesthetized and a microdialysis probe was inserted into the anterior chamber of one eye; the contralateral eye served as a control. At timed intervals after probe placement, a 100-microl sample of aqueous humor was aspirated from each eye to determine protein concentration. In vitro protein binding parameters were used to simulate the impact of protein concentration on propranolol disposition. To assess the influence of anesthesia, probes were implanted in the anterior chamber of each eye. After >5-day stabilization, conscious and anesthetized rabbits (n = 3/group) received a 200-microg topical dose of [3H]DL-propranolol in each eye; propranolol was assayed in probe effluent. RESULTS: Changes in aqueous humor protein concentrations were observed following probe insertion. Simulations demonstrated that the unbound propranolol AUC (approximately 2.4-fold) in aqueous humor should be reduced due to protein influx. Intraocular propranolol exposure in anesthetized rabbits was approximately 8-fold higher than in conscious rabbits, and approximately 1.9-fold higher than in rabbits without a post-surgical recovery period. CONCLUSIONS: Anesthesia and time-dependent aqueous humor protein concentrations may alter ocular pharmacokinetics, and must be taken into account in the design of microdialysis experiments.
Authors: Cheryl L Rowe-Rendleman; Shelley A Durazo; Uday B Kompella; Kay D Rittenhouse; Adriana Di Polo; Alan L Weiner; Hans E Grossniklaus; Muna I Naash; Alfred S Lewin; Alan Horsager; Henry F Edelhauser Journal: Invest Ophthalmol Vis Sci Date: 2014-04-28 Impact factor: 4.799