A pharmacokinetic study of a combination of beta adrenoreceptor antagonists – In the isolated perfused ovine eye

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.

Graphical abstractLipophilic beta adrenoreceptor antagonists penetrate to the posterior of the eye, where they bind to choroid and reside in the retina. Concentrations of CMax (axis in μg/g) obtained for atenolol (red column), timolol (blue column) and propranolol (green column).Figure optionsDownload full-size imageDownload as PowerPoint slide