title: Effects of dosing protocol on distribution of propranolol in periocular tissues after topical ocular instillation.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati , Cincinnati, OH , USA .
authors.forename: Hongzhuo
authors.initials: H
authors.lastname: Liu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yang
authors.forename: S Kevin
authors.initials: SK
authors.lastname: Li
authors.forename: Jinsong
authors.initials: J
authors.lastname: Hao
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005143:Eyelids / Q000187:drug effects* / Q000378:metabolism; D018324:Hemangioma, Capillary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007322:Instillation, Drug; D008297:Male; D009374:Neoplasms, Experimental; D009801:Oculomotor Muscles / Q000187:drug effects* / Q000378:metabolism; D009883:Ophthalmic Solutions; D011433:Propranolol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011817:Rabbits; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D011433:Propranolol
keywords: Distribution; hemangioma; ocular instillation; periocular tissue; propranolol