Effects of the preservative Purite® on the bioavailability of brimonidine in the aqueous humor of rabbits

To determine aqueous humor concentrations of brimonidine given the following ophthalmic formulations in female New Zealand White Rabbits: (1) BAK-preserved brimonidine tartrate 0.20% at a pH of 6.4; (2) BAK-preserved brimonidine tartrate 0.15% at a pH of 6.4, and (3) Purite((R))-preserved brimonidine tartrate 0.15% at a pH of 7.3. Eighteen (18) animals were given a 35-microL drop of formulation into each eye. Aqueous humor samples were collected at 9 time points over 8 hours. Brimonidine concentrations were quantified using LC-MS/MS. The C(max) was achieved between 0.33-0.67 hours postdosing for all 3 formulations. Mean C(max) after Purite-preserved brimonidine tartrate 0.15% was 88% higher than that after BAK-preserved brimonidine tartrate 0.15% (p = 0.040), and 44% higher than that after BAK-preserved brimonidine tartrate 0.20% (p = 0.0784). AUC(0-3 hr) values were comparable for all 3 formulations. Purite-preserved brimonidine tartrate 0.15% produced higher peak concentrations than BAK-preserved brimonidine tartrate 0.15%. It also had a concentration that was comparable to BAK-preserved brimonidine tartrate 0.20%. The differences in safety may result from the change in preservative.