Effect of single and multiple doses of 0.2% brimonidine tartrate in the glaucomatous Beagle

The objective of this study was to evaluate the changes in intraocular pressure (IOP) in glaucomatous dogs after instillations of 0.2% brimonidine once, twice and three times daily in single day studies, and after twice and three times daily for 4 days in multiple dose studies. We studied eight Beagles with inherited primary open angle glaucoma. Applanation tonometry (IOP), pupil size (PS) and heart rate (HR) measurements were obtained at 8 am, 10 am, 1 pm, 3 pm and 5 pm. The studies were divided into: eight glaucoma dogs and five of the eight dogs that demonstrated greater response to 0.2% brimonidine. Single-dose drug studies are divided into placebo (0.5% methylcellulose), 0.2% brimonidine administered once daily (8 am); twice daily (8 am and noon); and three times daily (8 am, noon and 5 pm). The 5-day multiple-dose studies included: day 1, no drug; and 4 days, 0.2% brimonidine instillations either twice daily (8 am and 2 pm) or three times daily (8 am, 2 pm and 9 pm). Statistical comparisons between drug groups included control (nondrug) and treated (placebo/0.2% brimonidine) eyes for both single- and multiple-dose studies. The mean +/- SEM diurnal decrease in IOP in the eight glaucomatous Beagles for the control and placebo eyes were 3.4 +/- 4.7 and 5.4 +/- 2.8 mmHg, respectively. The mean +/- SEM diurnal decrease in IOP after 0.2% brimonidine once, twice and three times daily was 6.4 +/- 3.5, 8.0 +/- 6.1 and 9.8 +/- 8.1 mmHg, respectively; this trend was not significant statistically. Significant miosis occurred starting 2 h postinstillations, and the resultant mean +/- SD pupil size was 2.7 +/- 0.3 mm. A significant decrease in heart rate also occurred (12%). In the five most responsive dogs the changes in PS and HR during these studies were similar to the larger group, but significant decreases in IOP occurred at most measurement times. In the multiple-dose study with 0.2% brimonidine twice daily the mean +/- SEM decrease in IOP for day 1 to day 4 was 5.0 +/- 1.3, 5.7 +/- 1.3, 1.4 +/- 3.3 and 4.9 +/- 1.3 mmHg, respectively. When 0.2% brimonidine was instilled three times daily the mean +/- SEM diurnal IOP decrease was from day 1 to day 4 and was 0.75 +/- 1.3, 2.4 +/- 1.5, 1.2 +/- 2.7 and 1.4 +/- 1.8 mmHg, respectively. The mean change in pupil diameter was 1.3 +/- 0.5 mm. Decrease in HR averaged 22%. In the same single-dose studies with the five most responsive dogs, PS and HR were similar, but the decreases in IOP were significant at more measurement intervals. We conclude that 0.2% brimonidine produces a decrease in IOP in dogs, a statistically significant miosis, and a reduced heart rate (12-22%). However, because of the limited drug-induced ocular hypotension, brimonidine should be combined with other drugs when used for the glaucomas in the dog.