Formulation effects on ocular absorption of brimonidine in rabbit eyes

Purite(TM) (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(R) (0.2% brimonidine tartrate/0.005% BAK, pH 6.4), Brimonidine-Purite (0.2% brimonidine tartrate/0.005% Purite(TM), 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 mul 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 C-max 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 mug-hr/mI (mean +/- SEM) for Brimonidine-Purite, Alphagan(R) and Brimonidine-PF, respectively. The corresponding C-max values were 2.69 +/- 0.72, 1.74 +/- 0.13, and 1.24 +/- 0.22 mug/ml (mean +/- SEM). Brimonidine-Purite provided significantly higher AUC(0-5hr) than Alphagan(R) (p < 0.05). No statistical significant difference in AUC(0-5hr). was found between Alphagan(R) 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(R) and 0.2% Brimonidine-PF, respectively.