Capillary electrophoretic analysis of brimonidine in aqueous humor of the eye and blood sera and relation of its levels with intraocular pressure

The aim of this study was the development of a capillary electrophoretic me thod for the determination of the levels of the selective alpha(2)-adrenerg ic receptor agonist brimonidine in aqueous humor of the eye and blood sera and their relation to its efficacy in reducing the intraocular pressure (IO P). Analysis of brimonidine was performed by capillary zone electrophoresis using 20 mM berate, pH 9.3, as operating buffer and detection at 255 nm. B rimonidine levels were determined in aqueous humor and blood sera from seve n patients admitted for cataract extraction following ocular administration of the ophthalmic Alphagan(TM) solution. Levels of brimonidine and IOP val ues were recorded for a 24 h period. Alphagan(TM) administration resulted i n a significant reduction of IOP, from within 30 min up to 4-5 h, whereafte r a stepwise increase was recorded until 24 h, where mean IOP value returne d to that before administration. The IOP reduction was related to the level s of brimonidine in aqueous humor, where maximal levels (80-100%) were obta ined within 1-3 h. A 50% amount of the solution was determined after 45 h, whereas it reached the minimum level after 12 h. Serum levels reached maxim um within 3-4 h, a 50% reduction was recorded in 12 h and minimum level in 24 h. It is concluded that brimonidine administration may significantly red uce IOP in patients when its level is maintained greater than or equal to 5 0% of the maximum present in aqueous humor, i.e within a 4-6 h period. Sinc e at this time the level of brimonidine in blood serum has reached maximum value, administration of brimonidine every 6 h may be used to obtain adequa te brimonidine levels to maintain a constantly lowered IOP. Copyright (C) 2 000 John Wiley & Sons, Ltd.