The aim of this study was the development of a capillary electrophoretic method for the determination of the levels of the selective alpha(2)-adrenergic receptor agonist brimonidine in aqueous humor of the eye and blood sera and their relation to its efficacy in reducing the intraocular pressure (IOP). Analysis of brimonidine was performed by capillary zone electrophoresis using 20 mM borate, pH 9.3, as operating buffer and detection at 255 nm. Brimonidine levels were determined in aqueous humor and blood sera from seven patients admitted for cataract extraction following ocular administration of the ophthalmic Alphagantrade mark solution. Levels of brimonidine and IOP values were recorded for a 24 h period. Alphagantrade mark administration resulted in a significant reduction of IOP, from within 30 min up to 4-5 h, whereafter a stepwise increase was recorded until 24 h, where mean IOP value returned to that before administration. The IOP reduction was related to the levels of brimonidine in aqueous humor, where maximal levels (80-100%) were obtained within 1-3 h. A 50% amount of the solution was determined after 4-5 h, whereas it reached the minimum level after 12 h. Serum levels reached maximum 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 reduce IOP in patients when its level is maintained >/=50% of the maximum present in aqueous humor, i.e within a 4-6 h period. Since 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 adequate brimonidine levels to maintain a constantly lowered IOP.
Copyright 2000 John Wiley & Sons, Ltd.