title: Formulation effects on ocular absorption of brimonidine in rabbit eyes.
abstract: Purite (stabilized oxychloro complex) and benzalkonium chloride (BAK) are preservatives. We investigated formulation effects on ocular absorption of brimonidine in rabbit eyes. The formulations compared were: Alphagan (0.2% brimonidine tartrate/0.005% BAK, pH 6.4), Brimonidine-Purite (0.2% brimonidine tartrate/0.005% Purite, pH 7.2), and Brimonidine-PF (0.2% brimonidine tartrate, preservative-free (PF), pH 6.4) solutions. The study was conducted in a cross-over fashion; albino rabbits (n = 18) were given a single 35 microl drop of each test formulation in each eye. Aqueous humor samples were collected at selected times post-dose from subgroups of 2 rabbits per timepoint and analyzed for brimonidine concentrations by LC-MS/MS. The AUC and Cmax were calculated. The results showed rapid ocular absorption of brimonidine, with peak concentrations at 0.33-1 hr. The AUC(0-5hr) values were 3.78 +/- 0.38, 2.77 +/- 0.22, and 2.49 +/- 0.22 microg-hr/ml (mean +/- SEM) for Brimonidine-Purite, Alphagan and Brimonidine-PF, respectively. The corresponding Cmax values were 2.69 +/- 0.72, 1.74 +/- 0.13, and 1.24 +/- 0.22 microg/ml (mean +/- SEM). Brimonidine-Purite provided significantly higher AUC(0-5hr) than Alphagan (p < 0.05). No statistical significant difference in AUC(0-5hr) was found between Alphagan and Brimonidine-PF. In conclusion, 0.2% Brimonidine-Purite was 1.4 and 1.5 times more ocularly bioavailable in rabbits than 0.2% Alphagan and 0.2% Brimonidine-PF, respectively.
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc, Irvine, California 92623-9534, USA. Acheampong_andrew@allergan.com
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Acheampong
authors.forename: David
authors.initials: D
authors.lastname: Small
authors.forename: Val
authors.initials: V
authors.lastname: Baumgarten
authors.forename: Devin
authors.initials: D
authors.lastname: Welty
authors.forename: Diane
authors.initials: D
authors.lastname: Tang-Liu
mesh_terms: D000042:Absorption; D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics*; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism; D019540:Area Under Curve; D001548:Benzalkonium Compounds; D001682:Biological Availability; D000068438:Brimonidine Tartrate; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D005260:Female; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D011810:Quinoxalines / Q000493:pharmacokinetics*; D011817:Rabbits
chemical_list: D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D011810:Quinoxalines; D000068438:Brimonidine Tartrate