Dose-dependent suppression of aqueous humor formation by timolol in the cynomolgus monkey

The effect of topical timolol on the fluorophotometrically determined aqueous humor formation rate in the cynomolgus monkey was studied. A timolol dose of 2.5, 5, 15, 30, 45, 90, or 180 $mUg was administered as a single topical dose to one eye of five monkeys. Postdrug flow rates were compared with no-drug baselines obtained on separate occasions. Our findings were that (a) topical timolol decreases aqueous humor formation rates in a dose-dependent fashion, with 30 $mUg and 50% flow suppression at or near the top of the single dose-response curve; (b) there is a significant contralateral effect, and only at extremely low doses can treated versus control eye effects be separated; and (c) doses as small as 2.5 $mUg can suppress aqueous formation by a statistically significant 20%. In the monkey, as in the human, timolol is a far more potent suppressor of aqueous formation than is generally realized, and standard clinical doses may in fact be overdoses in both species.