A pharmacokinetic study of a combination of beta adrenoreceptor antagonists - in the isolated perfused ovine eye

Eur J Pharm Biopharm. 2012 Feb;80(2):393-401. doi: 10.1016/j.ejpb.2011.11.006. Epub 2011 Nov 20.

Abstract

The treatment of posterior eye diseases, such as diabetic retinopathy and age-related macular degeneration, is of growing interest as the number of people affected by these conditions continues to rise. This study utilises the methods of cassette dosing and the perfused ovine eye model - to reduce animal usage and therefore animal time - to show that for a series of beta adrenoreceptor antagonists, lipophilicity is a key physicochemical property that governs drug distribution within the eye. Following intravitreal injection, lipophilic beta adrenoreceptor antagonists penetrate to the posterior eye, where they bind to the choroid and reside in the retina at greater concentrations than more hydrophilic beta adrenoreceptor antagonists, which preferentially penetrate to the anterior eye.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / chemistry
  • Adrenergic beta-Antagonists / pharmacokinetics*
  • Animals
  • Anterior Eye Segment / metabolism*
  • Atenolol / administration & dosage
  • Atenolol / chemistry
  • Atenolol / pharmacokinetics
  • Choroid / metabolism
  • Intravitreal Injections
  • Posterior Eye Segment / metabolism*
  • Propranolol / administration & dosage
  • Propranolol / chemistry
  • Propranolol / pharmacokinetics
  • Retina / metabolism
  • Sheep
  • Timolol / administration & dosage
  • Timolol / chemistry
  • Timolol / pharmacokinetics
  • Tissue Distribution

Substances

  • Adrenergic beta-Antagonists
  • Atenolol
  • Timolol
  • Propranolol