Comparison of the effects of aqueous and gellan ophthalmic timolol on peak exercise performance in middle-aged men.
OBJECTIVE
To compare the effects of 0.5% aqueous timolol and 0.5% timolol gellan on exercise performance in middle-aged men.


METHODS
We evaluated the effects of 0.5% aqueous timolol (timolol solution, administered twice daily, and a 0.5% timolol gellan suspension that forms a gel on application to the conjunctiva (timolol gellan), administered once 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 four times with ten-day intervals. After baseline testing, subjects were 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 immediately after testing were 0.91 +/- 0.51 ng/ml for timolol solution compared to 0.71 +/- 0.46 ng/ml for timolol gellan (P < .05). The change from 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 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 solution, and -8.5 +/- 7. 5 beats/min (P<.001) for timolol gellan. Pair-wise comparison demonstrated significantly less reduction in both resting (P < .05) and peak heart rate (P < .01) for timolol gellan vs timolol solution.


CONCLUSIONS
Although both treatments caused reductions in testing and peak heart rate, timolol gellan was associated with significantly less reductions. The significant difference in serum concentrations of timolol between the two treatments is strong evidence that the difference in heart rate response was caused by reduced systemic absorption with timolol gellan.
Dickstein
K
K
Cardiology Division, Central Hospital in Rogaland, Stavanger, Norway.
Aarsland
T
T
D000042:Absorption; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000368:Aged; D003228:Conjunctiva / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D005782:Gels; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011135:Polysaccharides, Bacterial; D013999:Timolol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D014867:Water
D000319:Adrenergic beta-Antagonists; D005782:Gels; D009883:Ophthalmic Solutions; D011135:Polysaccharides, Bacterial; D014867:Water; C048288:gellan gum; D013999:Timolol