Distribution of Brimonidine into Anterior and Posterior Tissues of Monkey, Rabbit, and Rat Eyes (original) (raw)
Research ArticleArticle
Drug Metabolism and Disposition April 2002, 30 (4) 421-429; DOI: https://doi.org/10.1124/dmd.30.4.421
Abstract
The objectives of the study were to evaluate the distribution of brimonidine (α2-adrenergic agonist) into anterior and posterior ocular tissues. Single or multiple doses of a 0.2 or 0.5% brimonidine tartrate solution were administered to one or both eyes of monkeys or to one eye of rabbits. Brimonidine was administered intraperitoneally to rats. After topical administration, [14C]brimonidine was rapidly absorbed into the cornea and conjunctiva and distributed throughout the eye. [14C]Radioactivity was higher and cleared more slowly in pigmented tissues (iris/ciliary body, choroid/retina, and optic nerve) than in nonpigmented tissues. Single and multiple dosing led to a similar drug distribution, with higher levels of brimonidine measured in pigmented tissues after multiple dosing. Most of the radioactivity extracted from ocular tissues represented unchanged brimonidine. In the rabbits and the monkey treated in only one eye, levels of radioactivity in the untreated eye were low, consistent with the low systemic levels and rapid drug clearance. Posterior ocular tissue concentrations of radioactivity exceeded systemic blood concentrations. The vitreous humor brimonidine concentrations in monkeys treated topically with 0.2% brimonidine tartrate was 82 ± 45 nM. Vitreous levels in rabbits confirmed the penetration of brimonidine to the posterior segment. Similar concentrations of brimonidine (22 to 390 nM) were measured in the vitreous and retina of rats injected intraperitoneally with brimonidine. Both topically applied and systemically administered brimonidine reach the back of the eye at nanomolar concentrations sufficient to activate α2-adrenergic receptors. The brimonidine levels achieved at the retina are relevant for neuroprotection models.
Footnotes
This work was supported by Allergan, Inc.
Abbreviations used are::
AGN 190342
5-bromo-6-(2-imidazolidinylideneamino)quinoxaline
LSC
liquid scintillation counting
HPLC
high-pressure liquid chromatography
AUC
area under the concentration-time curve
Eq
equivalents- Received October 19, 2001.
- Accepted January 4, 2002.
The American Society for Pharmacology and Experimental Therapeutics
Log in using your username and password
Purchase access
You may purchase access to this article. This will require you to create an account if you don't already have one.