Examination of the absorption and intra-ocular disposition of a model β-adrenergic antagonist using microdialysis

Purpose. The present study explored the utility of micrddialysis in the examination of aqueous humor disposition of topically vs. intracamerally administered -adrenergic antagonists in the dog and the rabbit. Methods. After initial experiments were conducted to estimate the quant ties of ³H-propranoloI required to obtain sufficient detection, DL-propranolol as the hydrochloride salt (5 μg/M-1 with respect to the base) in 0.9% saline was prepared wi h 289 uCi/mg (200 μg topical dose) or 18.3 μCi/mg (700 ng intracameral dose) 3H-('ropranolol. Four dogs (12-23 kg) and three rabbits (3.9-5.5 kg) were anesthetized, and a microdialysis probe (10-mm polycarbonate membrane) was implanted in the anterior chamber of one eye in the dog; probes were placed in both eyes of t ach rabbit. Probes were perfused with saline at a rate of 2 μl/min. ³H-propranolol was administered by intracameral injection or topically to one eye in dog. Each rabbit received intracameral 3H-propranolol in one eye and topical ³H-propranolol in the cor tralateral eye. Microdialysis probe effluent was collected every 5 min for ≥ 2.5 hr; inbound concentrations of propranolol were determined by liquid scintillation spectrrscopy. Model-independent pharmacokinetic parameters for each treatment phase were calculated. Results. Time to peak concentration of propranolol in aqueous humor was ∼87 min in the dog vs -54 min in the rabbit. The terminal rate constant in tie dog was -0.02 min^-1 vs ∼0.01 min^-1 in the rabbit. Bioavailability was 10 fold greate in rabbit than in the dog (-0.55 vs. -0.056). Conclusions. Microdialysis sampling of aqueous humor appears to be a reliable method for assessing aqueous humor ocular pharmacokinetics. Supported by NSF graduate research fellowship (KDR). C5. None.