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Pediatr Res. 2014 Oct;76(4):378-85. doi: 10.1038/pr.2014.108. Epub 2014 Jul 16.

Pharmacokinetics and local safety profile of propranolol eye drops in rabbits.

Author information

  • 1Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy.
  • 2Department of Chemistry, University of Florence, Florence, Italy.
  • 3Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
  • 4Department of Neurosciences, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
  • 5Department of Pediatric Neurosciences, "A. Meyer" University Children's Hospital, Florence, Italy.
  • 6Department of Pharmacy, "A. Meyer" University Children's Hospital, Florence, Italy.
  • 7Department of Pediatric Hematology and Oncology, "A. Meyer" University Children's Hospital, Florence, Italy.
  • 81] Department of Neurosciences, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Florence, Italy [2] Department of Pediatric Neurosciences, "A. Meyer" University Children's Hospital, Florence, Italy.

Abstract

BACKGROUND:

Oral propranolol, a nonselective β-blocker, is able to reduce the progression of retinopathy of prematurity in newborns, but it appeared unsafe. This study aimed to find, in rabbits, a propranolol eye drop concentration able to induce lower plasma but higher retinal concentrations than those obtained after oral administration.

METHODS:

Male New Zealand white rabbits were treated with oral propranolol (0.25 mg/kg/6 h) for 5 d, and propranolol concentrations were measured after 1, 2, 3, and 6 h in plasma, aqueous humor, vitreous humor, and retina. These concentrations were compared with those obtained after the administration of one drop of 25 μl of propranolol 0.1% prepared in saline, applied every 6 h to both eyes for 5 d. A Draize eye test and histological analyses were performed to assess eye drop tolerability.

RESULTS:

The administration of eye drops produced retinal concentrations similar to, but plasma concentrations significantly lower than, those measured after oral administration. The local tolerability profile was excellent.

CONCLUSION:

Propranolol eye drops are able to ensure high retinal and low plasma concentrations of propranolol, and this finding opens the perspective of possible topical treatment with propranolol in newborns with retinopathy of prematurity.

PMID:
25029260
[PubMed - in process]
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