Effects of dosing protocol on distribution of propranolol in periocular tissues after topical ocular instillation.

Curr Eye Res

Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH , USA .

Published: May 2015

Purpose: Our previous study demonstrated that topical ocular instillation can deliver effective concentrations of propranolol in the periocular tissues, and may be superior to oral propranolol in the treatment of periocular capillary hemangiomas. The objective of this study was to investigate the effects of dosing protocol on the distribution of propranolol in the periocular tissues and plasma after topical ocular instillation.

Methods: Each rabbit received propranolol 0.5% ophthalmic solution using one of the following dosing protocols: three drops of 50 μL, one drop of 50 μL, or one drop of 25 μL. The periocular tissues (e.g. eyelids and extraocular muscles) and blood were collected and assayed for propranolol at 1 h after dosing.

Results: Decreasing the concentration of eye drops (1% to 0.5%), decreasing the number of eye drops during dosing (three drops to one drop), or decreasing the instilled volume (50 µL to 25 µL) generally lowered the concentration of propranolol in the periocular tissues. Nevertheless, therapeutic levels of propranolol (> 0.4 μg/g) were delivered to the periocular tissues at 1 h after dosing using any of the three protocols examined. Dose-dependent concentrations in some periocular tissues and plasma were observed over the dose range of 0.125 mg to 1.5 mg. The plasma concentration of propranolol was not measurable when a single 25 μL of propranolol 0.5% was instilled in the eye.

Conclusions: The dosing protocol of topical ocular instillation can be tailored to achieve the desired therapeutic concentrations of propranolol in the periocular tissues while minimizing systemic exposure.

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http://dx.doi.org/10.3109/02713683.2014.952830DOI Listing

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