title: Pharmacokinetics and local safety profile of propranolol eye drops in rabbits.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Padrini
authors.affiliation: Department of Chemistry, University of Florence, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Isacchi
authors.affiliation: Department of Chemistry, University of Florence, Florence, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bilia
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
authors.affiliation: Department of Neurosciences, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lanzi
authors.affiliation: Department of Neurosciences, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Masini
authors.affiliation: Department of Pediatric Neurosciences, "A. Meyer" University Children's Hospital, Florence, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Della Bona
authors.affiliation: Department of Pharmacy, "A. Meyer" University Children's Hospital, Florence, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Calvani
authors.affiliation: Department of Pediatric Hematology and Oncology, "A. Meyer" University Children's Hospital, Florence, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ceccantini
authors.affiliation: 1] 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.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.affiliation: Medical Surgical Fetal-Neonatal Department, "A. Meyer" University Children's Hospital, Florence, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Filippi
mesh_terms: D060433:Administration, Ophthalmic; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D015169:Colony Count, Microbial; D008297:Male; D011433:Propranolol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011817:Rabbits
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol