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PubMedDate not supplied

A cross-over trial comparing once daily levobunolol with once and twice daily timolol.

The intraocular pressure (IOP) lowering efficacy of once-daily levobunolol 0.5% was compared with timolol 0.5% twice-daily and timolol 0.5% once-daily in 20 chronic open angle glaucoma and 5 ocular hypertensive patients. The design used was a randomised double blind cross-over trial with three periods each of 8 weeks separated by 2 weeks of no treatment. We found that following levobunolol a two week washout was not sufficient for the IOP to return to its original baseline level suggesting that levobunolol is a longer acting drug than timolol. Adjusting for this carryover effect, we found on significant difference in the IOP lowering effect among the three regimes (p = 0.53). Reduced cost, less ocular discomfort and better compliance are the main potential advantages of the once daily treatments.

Adrenergic beta-Antagonists↗

PubMed2003

Experience with COSOPT, the fixed combination of timolol and dorzolamide, gained in Swiss ophthalmologists' offices.

PURPOSE: In managing glaucoma through the lowering of intraocular pressure (IOP), beta-blockers (e.g. timolol) are commonly the drug of first choice, with other drugs added to control IOP such as carbonic anhydrase inhibitors (e.g. dorzolamide). The present survey was instigated to assess the COSOPT (fixed combination of topical timolol and topical dorzolamide) prescription behaviour of Swiss office-based ophthalmologists and to evaluate the IOP-lowering efficacy of COSOPT under real-life private practice conditions. METHODS: A survey was conducted in Swiss ophthalmologist practices. Ophthalmologists were asked to report their experience with COSOPT therapy prescribed to patients with glaucoma or ocular hypertension. Parameters recorded were: patient demographics, IOP, reason for choosing COSOPT, continuation of COSOPT therapy after completion of the survey and, if stopped, reason for discontinuation, and spontaneously occurring side-effects. All entries were optional. Since the purpose of this survey was to obtain a realistic picture of daily practice in Swiss ophthalmologists' offices, no guidelines with regard to measurement of IOP, time between visits and actual treatment were given. RESULTS: Data of 733 patients were included in this analysis. COSOPT as sole therapy was prescribed to 538 patients (74%), whereas 120 (16%) were put on a combination regimen of COSOPT + latanoprost. The remaining 75 patients (10%) received combinations of COSOPT with other ocular hypotensives. When assessing those patients put on COSOPT alone, IOP reduction in new, previously untreated patients was 10.8 mmHg (average), 5.4 mmHg (average) in upgrades from previous monotherapy and 2.7 mmHg after switch from free combination therapy. Patients treated with a combination of COSOPT + latanoprost showed an IOP reduction of 27 mmHg (new, previously untreated patients), 7.6 mmHg (upgrades from monotherapy) and 3.8 mmHg (switches from previous free combination regimen). Therapy was continued in 89% of all patients overall and in 91% of new patients treated with COSOPT alone (first line). 6.8% stopped therapy due to side-effects. CONCLUSIONS: COSOPT, the fixed combination of 0.5% timolol and 2% dorzolamide, is broadly prescribed to new, upgrade and switch patients in Switzerland. COSOPT therapy is well-tolerated and highly efficacious for patients requiring strong IOP lowering. Nine out ten patients stay on therapy after 1-2 months of treatment.

Adolescent↗

PubMed2005

Timolol LA: a double-masked, active-controlled, randomized, crossover, comfort, ocular safety, and systemic bioavailability study in healthy volunteers.

PURPOSE: A new formulation of timolol with sorbic acid, timolol-LA (TLA) (Istaloldagger), has been developed which increases its ocular bioavailability. In the present study, we desired to evaluate the ocular comfort and systemic bioavailability of TLA in healthy volunteers in comparison to standard timolol maleate ophthalmic solution (TIM). METHODS: This study was a randomized, double-masked, active-controlled, crossover evaluation of 0.5% TLA and 0.5% TIM, bid, in 12 normal healthy volunteers. Visits were at Days 0, 1, 2, 4 and 8 in each period, and there was a minimum 7 day interperiod washout. RESULTS: At all three post-dosing evaluation times (Day 1: Peak, Day 8: Trough, and Day 8: Peak), the 95% confidence interval for the difference between TLA and TIM was not more than 0.37 ng/mL. After administration of TLA, there was a greater incidence of burning/stinging and tearing, but not foreign body sensation, relative to TIM. In general, most symptoms were mild in intensity, and no subject discontinued treatment due to ocular discomfort. Both treatments decreased IOP to a similar level. CONCLUSION: TLA was relatively comfortable, with a safety profile consistent with further clinical development, and, with bid dosing (exaggerated [2X] that anticipated for clinical use), had a systemic bioavailability similar to that of TIM 0.5%, bid. The incidence of burning and stinging was higher with TLA than with TIM, although reports were mild in severity and did not result in any patient discontin uations. Although the results are of interest, further evaluation in a larger trial may be warranted.

Adrenergic beta-Antagonists↗

PubMed1991

Adrenergic modulation of preoperative anxiety: a comparison of temazepam, clonidine, and timolol.

To assess the influence of adrenergic modulation on preoperative anxiety, we used a randomized, double-blind, placebo-controlled trial to compare temazepam, clonidine, and timolol as preanesthetic medications in patients undergoing minor orthopedic surgery. All the active treatments resulted in less preoperative anxiety than the placebo (control) did. Induction of anesthesia was smoother in all the treated patients compared with the control group. Recovery was slowest in the temazepam and clonidine groups, but there were no significant differences between the groups after 90 min. Cardiovascular changes were most marked in the timolol group. Pain scores were lower in the temazepam and clonidine series in the early postoperative period. Neither clonidine nor timolol offers any major advantage over temazepam for premedication in these patients.

Adult↗

PubMed1983

Respiratory arrest following first dose of timolol ophthalmic solution.

Within 30 minutes of the administration of his first dose of timolol ophthalmic solution, a 67-year-old man with stable chronic obstructive pulmonary disease experienced severe dyspnea leading to respiratory arrest. He recovered after endotracheal intubation and mechanical ventilation. Patients with bronchospastic pulmonary disease who are candidates for therapy with timolol ophthalmic solution should receive their first dose under medical supervision and should have continued close medical follow-up for as long as they receive timolol.

Aged↗

PubMed1979

Timolol: a review of its therapeutic efficacy in the topical treatment of glaucoma.

Timolol maleate is a nonselective beta-blocking drug used for the topical treatment of increased intraocular pressure in patients with chronic open angle glaucoma. In comparative studies it has had a somewhat greater ocular hypotensive effect than the sympathomimetic agent adrenaline (epinephrine), or lower to medium concentrations (up to 4%) of the miotic drug pilocarpine, usually lowering intraocular pressure by about 30 to 35% (absolute pressure reduction). Timolol has been well tolerated by most patients, producing fewer subjective complaints than the comparison drugs, and objective measurements of ophthalmic status have not revealed any marked changes. Although some patients have been treated for extended periods without serious adverse effects or loss of effectiveness, further published reports in larger numbers of patients treated over several years are needed to confirm the drug's apparent long term safety and continued efficacy. Nevertheless, on the basis of present evidence, timolol appears to represent an important advance in the topical treatment of glaucoma.

Glaucoma↗

PubMedDate not supplied

Manufacture of polyalkylcyanoacrylate nanoparticles with pilocarpine and timolol by micelle polymerization: factors influencing particle formation.

Nanoparticles with pilocarpine and timolol were produced by micelle polymerization. The influence of manufacturing temperature, type of monomer, drug concentration and ethylcyanoacrylate concentration on the particle size were investigated with a Coulter Nano Sizer. The nanoencapsulation succeeded only with the pilocarpine or timolol base, not with the salts of these drugs. Different micelle formation in aqueous medium compared with organic solvents was evidently responsible for this phenomenon. The particle formation was affected both by the manufacturing temperature and the type of monomer. The smallest particles were produced at lower temperatures and with the most lipophilic monomers. The monomer and drug concentration had very little influence on the particle size. The nanoparticles made with pilocarpine were, in general, much bigger than those made with timolol.

Colloids↗

PubMed1999

[Interstitial lung disease induced by timolol eye solution].

Timolol maleate is a beta-blocker widely used in topical administration for open angle glaucoma. We report a case of interstitial pneumopathy which developed in a 58-year-old patient who was given timolol eyedrops (2 drops b.i.d. since 1986). The patient presented with cough and dyspnea and was found to have a restrictive disorder leading to hypoxemia (68 mmHg at rest and 51 mmHg during exercise). Bronchial lavage fluid had high lymphocyte (28%) and neutrophil (7%) counts. Transbronchial biopsies demonstrated moderate fibrous thickening of the interalveolar walls. Timolol eyedrops were stopped. Three months later, the patient was asymptomatic with normal lung function, chest x-ray and thoracic CT-scan.

Adrenergic beta-Antagonists↗

PubMed2000

[Combined effect of topical latanoprost and timolol on retinal blood flow and tissue circulation in the optic nerve head in cynomolgus monkeys].

PURPOSE: To evaluate the combined effect of topical latanoprost and timolol on the retinal blood flow and the tissue circulation of the optic nerve head (ONH) in cynomolgus monkeys. MATERIALS AND METHODS: 30 microliters of latanoprost (0.005%) was instilled once daily and timolol (0.5%) twice daily into one eye, and physiological saline as a control into the other eye of 8 cynomolgus monkeys for 6 days. Blood velocity through the retinal veins was measured using a KOWA Laser Speckle Blood Flow Meter. The ONH tissue blood velocity normalized blur (NBONH) was measured using a Laser Speckle Tissue Circulation analyzer. Retinal blood flow, NBONH, intraocular pressure (IOP), blood pressure, and pulse rate were measured before the first instillation, 4 hours after the first instillation on the 2nd experimental day, and 4 hours after the last instillation. RESULTS: After the first instillation on the 2nd experimental day, the retinal blood flow was decreased to below the baseline, but 6-day instillation caused no significant change from the baseline. Six-day instillation increased the NBONH in the treated eyes by 10% from the baseline and by 7% from that in the fellow control eye. After 6-day instillation, the IOP was lowered by 7.8 +/- 2.7 (mean +/- standard deviation) mmHg and 3.6 +/- 4.3 mmHg in the treated and control eyes, respectively. CONCLUSION: The results suggest that 6-day instillation of latanoprost once daily and timolol twice daily has no significant effect on the retinal blood flow, and significantly increases the ONH tissue blood velocity in monkey eyes.

Animals↗

PubMed2002

Serum lipid profile and timolol gel.

Topical use of timolol eye drops in the management of glaucoma is associated with various systemic side effects including alteration of lipid profile with increase in cardiovascular risk factors. Change over to timolol gel altered results in normalisation of altered lipid profile with decrease in cardiovascular risk factors. The decrease seen is attributable to lack of systemic absorption of timolol gel.

Administration, Topical↗

PubMed2003

Rapid and sensitive HPLC method for the simultaneous determination of dorzolamide hydrochloride and timolol maleate in eye drops with diode-array and UV detection.

A rapid and sensitive HPLC method has been developed for the simultaneous determination of dorzolamide hydrochloride and timolol maleate. The drugs were monitored with a diode-array detector at two fixed wavelengths (lambda = 250.0 nm for dorzolamide hydrochloride and 300.0 nm for timolol maleate). Liquid chromatography was performed on a RP-YMC pack ODS A-132 C18 (5 microm, 15 cm x 6.0 mm) column and the mobile phase consisted of an acetonitrile: phosphate buffer (pH 2.5): methanol (5:85:10 v/v/v) mix and a flow rate of 1.2 ml x min(-1). The linearity of the method ranged between 4.0-45.0 microg x ml(-1) for dorzolamide hydrochloride and and 2.0-20.6 microg x ml(-1) for timolol maleate in binary mixture. The procedure was successfully applied to the determination of these compounds in pharmaceutical preparations and gave a high recovery, good accuracy and precision without any interference by the excipients.

Adrenergic beta-Antagonists↗

PubMed1992

Effects of timolol and acetazolamide on intraocular pressure elevation following argon laser iridotomy.

To study the effect of hypotensive agents on intraocular pressure elevation following argon laser iridotomy, 0.5% timolol maleate topically and acetazolamide 125 mg orally were given in 39 eyes, one hour prior to laser iridotomy, with 29 eyes serving as the control. The mean pressure two hours after laser iridotomy was 18.9 +/- 7.2 mmHg in the control group and 12.8 +/- 3.9 mmHg in the pretreated group. Ocular pressure was elevated from the baseline pressure of the prelaser status in two eyes (5%) only in the timolol-acetazolamide treated group and in 16 eyes (55%) in the control group. The pressure elevation two hours after laser iridotomy was significantly less in the timolol-acetazolamide pretreated group.

Acetazolamide↗

PubMed1992

[Does timolol modify retinal hemodynamics in patients with normal pressure glaucoma?].

In 31 patients with normal-pressure glaucoma, retinal blood flow, diameter of the retinal vessels and velocity were measured with 2-point fluorometry and automatic measurement of the diameters before and after administration of 0.5% timolol over 2 weeks. After timolol therapy the tension was significantly decreased (before therapy: 18.26 +/- 2.50; after therapy: 15.61 +/- 2.56 mm Hg, P < or = 0.01). The arterial and venous diameters and blood flow were nearly unchanged, but a slight increase in the arterial and venous velocity was noted. We conclude that timolol does not significantly influence the retinal hemodynamics in patients with normal-pressure glaucoma.

Adult↗

PubMed1978

[Effect of daily instillations of timolol on the nycthemeral tension in subjects with chronic open-angle glaucoma (author's transl)].

This study included 22 patients with chronic open-angle glaucoma who were treated with either 0.25% or 0.5% timolol. The results showed that a single daily instillation of 0.25% or 0.5% timolol was effective, without producing any side-effects. It was interesting to note that timolol caused the tension peaks to disappear, the nycthemeral graph curve becoming plateau-shaped.

Adult↗

PubMed2006

Promoting effect of borneol on the permeability of puerarin eye drops and timolol maleate eye drops through the cornea in vitro.

Studies on the influence of borneol on the penetration of puerarin eye drops and timolol maleate eye drops through the cornea, and evaluation of the ocular irritability were conducted to provide a theoretical basis for the application of borneol in enhancing corneal permeability. The cornea penetrative experiment in vitro was conducted to observe the quantitative change of puerarin and timolol maleate penetrated through the cornea after administering different dosages of borneol. The corneal hydration level and blinking frequency were recorded as irritability indexes in vitro and in vivo. The steady-flow J of high, middle and low dosage groups of puerarin eye drops with borneol were increased by 49%, 32%, 5% respectively, and permeability parameter Kp increased by 49%, 32%, 5% respectively, as compared to that of the control group. The steady-flow J of high dosage group of timolol maleate eye drops with borneol was increased by 5%; middle and low dosage groups with borneol were decreased by 6%, 3% respectively. The permeability parameter Kp of high dosage group increased by 5%, while middle and low dosage groups with borneol were decreased by 6%, 3% respectively, as compared to that of the control group. Evaluation showed no ocular irritability caused by borneol. The results of this study suggest that the promoting effect of borneol on the permeability of drugs through the cornea in vitro is selective, which indicates that borneol has the potential to be used as an ophthalmic penetration enhancer.

Adrenergic beta-Antagonists↗

PubMed1991

[Additive effect of timolol and the local carbonic anhydrase inhibitor MK-417 (sezolamide)].

MK-417 (sezolamide) is a topically active carbonic anhydrase inhibitor. The effect of additional treatment with sezolamide 1.8% twice daily to patient already receiving timolol 0.5% twice daily was investigated. For this purpose, 12-h diurnal curves were used in a double-masked, randomized, placebo-controlled, parallel study in 36 patients with bilateral primary open angle glaucoma or ocular hypertension who during beta blocker therapy had intraocular pressures (IOP) greater than or equal to 22 mmHg. For 15 days patients received sezolamide or placebo 10 min after 0.5% timolol given at 8 a.m. and 8 p.m. On treatment day 15, this addition of sezolamide twice daily induced a further mean decrease in IOP of approximately 4 mm Hg (about 15%) at 1, 2 and 4 h and of approximately 2-3 mm Hg at 0, 6, 8, 10 and 12 h after drug administration, thus demonstrating a partial additive effect of sezolamide and timolol. Thus, sezolamide may be a useful addition to the treatment of glaucoma in patients not adequately controlled by beta blocker therapy.

Aged↗

PubMed1991

The Glaucoma Laser Trial: 4. Contralateral effects of timolol on the intraocular pressure of eyes treated with ALT. GLT Research Group.

Several reports have documented a contralateral intraocular pressure (IOP) lowering effect after unilateral instillation of timolol. Data derived from the Glaucoma Laser Trial (GLT), a randomized trial of the efficacy and safety of argon laser trabeculoplasty (ALT) as compared with the efficacy and safety of topical medications as initial therapy for primary open-angle glaucoma (POAG), demonstrated an estimated mean pressure reduction of 0.5 mm Hg in the contralateral eye that had received ALT. This contralateral effect is smaller than that observed in other studies of POAG patients. Lower initial IOP, longer duration of treatment with timolol, and/or improved outflow facility modulation in the ALT-treated eyes may be responsible for the smaller contralateral effect of timolol observed in the GLT patients.

Adult↗

PubMedDate not supplied

[Hypotensive effects of timolol in 86 patients (author's transl)].

Antihypertensive action of timolol (MK 950) was studied in 86 outpatients with essential, uncomplicated hypertension. Timolol is an effective hypotensive drug with significant lowering pressor effect. Timolol was given alone in 53 cases and in association with other hypotensive drugs in 33 cases: the mean dose was 20 mg daily for 8 months. At the end of treatment the mean diastolic pressure recumbert, standing, and after exercise had decreased by 10.2, 9.2 and 11 mmHg. Cardiac frequency had decreased by 13, 24 and 29 p. min lying, standing and after exercise. Side effects were rare, with cessation of treatment only in 4 cases.

Adolescent↗