RT Journal Article SR Electronic T1 Comparative ocular pharmacokinetics of brimonidine after a single dose application to the eyes of albino and pigmented rabbits. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 708 OP 712 VO 23 IS 7 A1 A A Acheampong A1 M Shackleton A1 D D Tang-Liu YR 1995 UL http://dmd.aspetjournals.org/content/23/7/708.abstract AB 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)