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 oftopical 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.
RCT Entities:
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.
Authors: Xu Wen Ng; Kerh Lin Liu; Amutha Barathi Veluchamy; Nyein Chan Lwin; Tina T Wong; Subbu S Venkatraman Journal: Drug Deliv Transl Res Date: 2015-10 Impact factor: 4.617
Authors: Nicole L Pratt; Emmae N Ramsay; Lisa M Kalisch Ellett; Tuan A Nguyen; Elizabeth E Roughead Journal: J Ophthalmol Date: 2015-03-22 Impact factor: 1.909