title: Comparative ocular pharmacokinetics of brimonidine after a single dose application to the eyes of albino and pigmented rabbits.
abstract: Brimonidine is a potent ocular hypotensive drug. The ocular pharmacokinetics of 14C-brimonidine in albino and pigmented rabbits were compared after ocular instillation of a 35-microliters drop of a 0.5% 14C-brimonidine solution. Ocular drug and metabolite concentrations were measured as total radioactivity and by a selective HPLC method. Rapid ocular absorption resulted in peak drug concentrations in aqueous humor of 2.16 +/- 0.75 micrograms/ml (mean +/- SD) and 1.52 +/- 0.38 micrograms/ml at 0.67 hr postdosing in albino and pigmented rabbits, respectively. Drug elimination from aqueous humor was rapid initially with a half-life of 1 hr in rabbits, followed by a slower decline phase in pigmented rabbits. Radioactivity concentration in iris-ciliary body of albino rabbit reached a peak of 5.04 micrograms-eq/g at 40 minutes and declined to 0.10 micrograms-eq/g at 6 hr postdosing with a half-life of 1 hr. The radioactivity concentrations in pigmented iris-ciliary body rose to a peak of 20.1 micrograms-eq/g at 1.5 hr and stayed relatively steady for at least 4 hr before declining slowly to 0.43 micrograms-eq/g 90 days postdose. The terminal half-life of brimonidine in pigmented iris-ciliary body was 160 hr. Three metabolites were detected in the conjuctiva and iris-ciliary body, and brimonidine was the major drug-related substance in aqueous humor and iris-ciliary body. The results indicate that brimonidine is absorbed rapidly into rabbit eyes, metabolized in ocular tissues, and has significant affinity for melanin-containing tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacokinetics, Allergan Pharmaceuticals, Irvine, CA 92713-9534, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Acheampong
authors.forename: M
authors.initials: M
authors.lastname: Shackleton
authors.forename: D D
authors.initials: DD
authors.lastname: Tang-Liu
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D016115:Albinism, Oculocutaneous / Q000378:metabolism; D000818:Animals; D000068438:Brimonidine Tartrate; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005123:Eye / Q000378:metabolism*; D005260:Female; D009883:Ophthalmic Solutions; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D011810:Quinoxalines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D011817:Rabbits
chemical_list: D000316:Adrenergic alpha-Agonists; D002250:Carbon Radioisotopes; D009883:Ophthalmic Solutions; D011810:Quinoxalines; D000068438:Brimonidine Tartrate