Efficacy and systemic side-effects of topical 0.5% timolol aqueous solution and 0.1% timolol hydrogel.

PURPOSE

The objective of this randomized, double-blind, controlled crossover trial was to compare 0.1% timolol hydrogel formulation eyedrops with 0.5% timolol aqueous solution in terms of systemic effects, hypotensive efficacy and pharmacodynamics.

METHODS

Twenty-four healthy subjects underwent careful ocular, cardiovascular and pulmonary function evaluation before and after 2 weeks of topical treatment with 0.1% timolol hydrogel or 0.5% aqueous timolol maleate. Intraocular pressure (IOP), heart rate, blood pressure, forced expiratory volume and plasma levels of timolol were measured.

RESULTS

There was a statistically significant difference in the systemic absorption of timolol between these two ophthalmic timolol solutions. The peak concentration and mean area under the plasma drug concentration-time curve (AUC) were about 10-fold higher after 0.5% timolol aqueous solution. The mean peak heart rate during exercise was reduced by 19 bpm (SD 6.4 bpm) after 0.5% timolol aqueous solution and by only 4.6 bpm (SD 3.8 bpm) after 0.1% timolol hydrogel (p < 0.0001). There was no difference between the two formulations in efficacy in reducing IOP. No differences between treatments were found in respect of pulmonary function.

CONCLUSIONS

The lower timolol concentration in the hydrogel vehicle and its better bioavailability resulted in reduced systemic absorption and side-effects without loss of efficacy.