COMPARISON OF THE EFFECTS OF AQUEOUS AND GELLAN OPHTHALMIC TIMOLOL ONPEAK EXERCISE PERFORMANCE IN MIDDLE-AGED MEN

PURPOSE: To compare the effects of 0.5% aqueous timolol and 0.5% timol ol gellan on exercise performance in middle-aged men. METHODS: We eval uated the effects of 0.5% aqueous timolol (timolol solution), administ ered twice daily, and a 0.5% timolol gellan suspension that forms a ge l on application to the conjunctiva (timolol gellan), administered onc e daily, on exercise performance in 42 healthy men with a mean age of 58 years (range, 55 to 65 years). Serum concentrations of timolol were assayed. Subjects exercised maximally on an upright cycle ergometer f our times with ten day intervals. After baseline testing, subjects wer e randomly assigned and crossed over in a double-masked manner to two and a half days of treatment with placebo, 0.5% timolol solution, and 0.5% timolol gellan. RESULTS: The serum timolol concentrations immedia tely after testing were 0.91 +/- 0.51 ng/ml for timolol solution compa red to 0.71 +/- 0.46 ng/ml for timolol gellan (P < .05). The change fr om baseline in resting heart rate was -1.8 +/- 9.3 beats/min (P = .23) for placebo, -11.0 +/- 9.6 beats/min (P < .001) for timolol solution, and -8.5 +/- 7.5 beats/min (P < .001) for timolol gellan. The change from baseline in peak heart rate was -0.1 +/- 7.3 beats/min (P = .92) for placebo, -15.6 +/- 5.6 beats/min (P < .001) for timolol solution, and -11.9 +/- 8.0 beats/min (P < .001) for timolol gellan. Pair-wise c omparison demonstrated significantly less reduction in both resting (P < .05) and peak heart rate (P < .01) for timolol gellan vs timolol so lution. CONCLUSIONS: Although both treatments caused reductions in res ting and peak heart rate, timolol gellan was associated with significa ntly less reductions. The significant difference in serum concentratio ns of timolol between the two treatments is strong evidence that the d ifference in heart rate response was caused by reduced systemic absorp tion with timolol gellan.