The purpose of the study was to compare the systemic safety and risk-benefit ratio of 0.1% timolol hydrogel and 0.5% aqueous timolol eye drops in the treatment of glaucoma.
An 8-week randomised, double-blind, cross-over, multicentre study. A total of 25 patients with primary open-angle glaucoma, exfoliation glaucoma, or ocular hypertension was enrolled. After completing a wash-out period, patients were randomly chosen to receive either 0.1% timolol hydrogel once daily or 0.5% aqueous timolol eye drops twice daily. Intraocular pressure and heart rate during rest and exercise, head-up tilt test results, spirometry readings, and plasma concentrations of timolol were recorded. The risk-benefit ratio was determined by calculating the ratio between several heart rate endpoints and the change in intraocular pressure (IOP).
The mean drug-induced change in the peak heart rate during exercise was -13.5 beats/min (SD 7.6) in the 0.5% aqueous timolol group and -5.1 beats/min (SD 6.7) in the 0.1% timolol hydrogel group (P < 0.001; 95% CI 4.06-12.18). There was no significant difference in the IOP-reducing efficacy between these compounds. The risk-benefit ratio was significantly improved when 0.1% timolol hydrogel was used, compared with 0.5% aqueous timolol in the exercise test. In the head-up tilt test the risk-benefit ratio was significantly improved at rest (P < 0.05), at 1 min (P < 0.05) and at 5 min (P < 0.001) after patients had received 0.1% timolol hydrogel. There were, however, no differences in spirometry readings. After patients had been treated with 0.1% timolol hydrogel, plasma concentrations of timolol were 1/6 (at peak) and 1/50 (at trough) of those of 0.5% aqueous timolol.
Drug-induced changes in the peak heart rate, and head-up tilt test results as well as plasma concentrations of timolol, were significantly more pronounced after treatment with 0.5% aqueous timolol than with 0.1% timolol hydrogel. Because of the statistically similar IOP-reducing efficacy of these formulations the risk-benefit ratio was significantly improved when patients used 0.1% timolol hydrogel instead of 0.5% aqueous timolol.
2006. Vol. 244, no 11, 1491-1496 p.