Journal
CURRENT EYE RESEARCH
Volume 40, Issue 6, Pages 638-645Publisher
INFORMA HEALTHCARE
DOI: 10.3109/02713683.2014.952830
Keywords
Distribution; hemangioma; ocular instillation; periocular tissue; propranolol
Categories
Funding
- University Research Council at the University of Cincinnati
- Research to Prevent Blindness
- Quest for Vision Fund
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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 mu L, one drop of 50 mu L, or one drop of 25 mu L. 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 mu L to 25 mu L) generally lowered the concentration of propranolol in the periocular tissues. Nevertheless, therapeutic levels of propranolol (>0.4 mu g/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 0.125mg to 1.5 mg. The plasma concentration of propranolol was not measurable when a single 25 mu L 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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