Efficacy and systemic side-effects of topical 0.5% timolol aqueous solution and 0.1% timolol hydrogel.
OBJECTIVE
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.
Uusitalo
Hannu
H
Department of Ophthalmology, Tampere University Hospital, Tampere, Finland. hannu.uusitalo@uku.fi
Niño
Juanita
J
Tahvanainen
Kari
K
Turjanmaa
Väinö
V
Ropo
Auli
A
Tuominen
Juhani
J
Kähönen
Mika
M
D000042:Absorption; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012129:Respiratory Function Tests; D013999:Timolol / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D020100:Hydrogels; D009883:Ophthalmic Solutions; D013999:Timolol