Formulation effects on ocular absorption of brimonidine in rabbit eyes.
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.
Acheampong
Andrew A
AA
Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc, Irvine, California 92623-9534, USA. Acheampong_andrew@allergan.com
Small
David
D
Baumgarten
Val
V
Welty
Devin
D
Tang-Liu
Diane
D
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
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D011810:Quinoxalines; D000068438:Brimonidine Tartrate