Abstract | PURPOSE: We compared ocular and systemic pharmacokinetics of brimonidine and dexamethasone following a single intravitreal dose in animals with blood-retinal barrier (BRB) breakdown and in healthy controls. METHODS: RESULTS: In rabbits, brimonidine and dexamethasone exposure, as assessed by area under the drug concentration-time curve (AUC) in aqueous humor, retina, and choroid, was lower in disease than control animals, with a greater difference observed for dexamethasone than brimonidine. In monkeys, dexamethasone exposure was lower in disease than control animals for the central retina/choroid and peripheral choroid, whereas brimonidine exposure was lower in disease animals only in the central retina/choroid. Plasma exposure to both drugs was comparable between control and disease animals in both species. CONCLUSIONS: In animal models with a breakdown of the blood-retina barrier, drug clearance could be increased, resulting in lower drug concentration in ocular tissues compared to normal animals. However, the extent of difference may be compound- and disease model-specific. Therefore, extrapolation of ocular pharmacokinetic data obtained in normal animals to disease models for the purpose of pharmacokinetic/pharmacodynamic data analysis should be performed with caution.
|
Authors | Jie Shen, Chandra Durairaj, Ton Lin, Yan Liu, James Burke |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 55
Issue 2
Pg. 1056-66
(Feb 20 2014)
ISSN: 1552-5783 [Electronic] United States |
PMID | 24448267
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Adrenergic alpha-2 Receptor Agonists
- Glucocorticoids
- Quinoxalines
- Brimonidine Tartrate
- Dexamethasone
|
Topics |
- Adrenergic alpha-2 Receptor Agonists
(pharmacokinetics)
- Animals
- Aqueous Humor
(metabolism)
- Biological Availability
- Blood-Retinal Barrier
(metabolism)
- Brimonidine Tartrate
- Capillary Permeability
- Choroid
(metabolism)
- Choroidal Neovascularization
(metabolism)
- Chromatography, High Pressure Liquid
- Dexamethasone
(pharmacokinetics)
- Female
- Glucocorticoids
(pharmacokinetics)
- Intravitreal Injections
- Macaca fascicularis
- Models, Animal
- Quinoxalines
(pharmacokinetics)
- Rabbits
- Retina
(metabolism)
- Tandem Mass Spectrometry
- Vitreous Body
(metabolism)
|