Effects of the preservative purite on the bioavailability of brimonidine in the aqueous humor of rabbits.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dong
Jennifer Q
JQ
Departments of Pharmacokinetics and Drug Metabolism, Allergan, Inc., Irvine, CA, USA.
Babusis
Darius M
DM
Welty
Devin F
DF
Acheampong
Andrew A
AA
Tang-Liu
Diane
D
Whitcup
Scott M
SM
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D001548:Benzalkonium Compounds / Q000493:pharmacokinetics; D001682:Biological Availability; D000068438:Brimonidine Tartrate; D002626:Chemistry, Pharmaceutical; D004347:Drug Interactions; D005260:Female; D011310:Preservatives, Pharmaceutical / Q000493:pharmacokinetics*; D011810:Quinoxalines / Q000493:pharmacokinetics*; D011817:Rabbits
D001548:Benzalkonium Compounds; D011310:Preservatives, Pharmaceutical; D011810:Quinoxalines; D000068438:Brimonidine Tartrate