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PubMed1980

[Timolol eyedrops in ophthalmological practice].

Fifty-eight glaucoma patients (105 eyes) of an ophthalmological practice were treated with Timolol eyedrops (0.1%-0.5% once or twice daily) over a long-term period. In group 1 - without pre-treatment (12 patients) pressure was lowered by 34%. In group II, glaucoma patients who were insufficiently stabilized by conservative treatment. Timolol was added to the glaucoma medication and thus a further pressure decrease of 27% was achieved. Group III comprised 24 glaucoma patients who, although their intraocular pressure was satisfactorily controlled, had problems with their medication. After having been switched to Timolol alone they presented a further decrease in IOP of 22%. Group IV comprised those patients resistant to Timolol therapy (six patients; 10%) who showed no further reduction in IOP--neither with Timolol alone nor in combination with other glaucoma medication. Advantages and slight disadvantages of Timolol therapy were discussed. Timolol is the only local glaucoma medication without ascertainable side-effects and thus represents a gain for the therapeutic spectrum of the practitioner.

Adult↗
PubMed1989

Ophthalmic epinephrine, phenylephrine, and pilocarpine affect the systemic absorption of ocularly applied timolol.

Ocularly applied timolol eyedrops may cause serious systemic side-effects in some patients. In this study we evaluated the effects of pretreatment with epinephrine and pilocarpine eyedrops on systemic absorption of ophthalmic timolol. Epinephrine decreased the systemic absorption of timolol, while pilocarpine increased the peak concentrations of timolol in plasma. When applied in the same solution with timolol, pilocarpine had no effect and phenylephrine decreased the systemic absorption of timolol. The observed effects were due to the conjunctival and nasal vasoconstricting effects of epinephrine and phenylephrine and to the vasodilating effects of pilocarpine. These pharmacokinetic interactions demonstrate the importance of the conjunctival and nasal blood flow in the systemic absorption of timolol.

Absorption↗
PubMed1995

Comparison of concentration-time profiles of levobunolol and timolol in anterior and posterior ocular tissues of albino rabbits.

The potential effects of anti-glaucoma drugs, such as levobunolol and timolol, on blood flow in the posterior segment of the eye are of great interest in terms of changes in optic nerve head perfusion and prevention of visual field loss. These effects are related to the rate and extent of their absorption into the site of action. In this study, the concentrations of timolol and levobunolol in the aqueous humor, iris-ciliary body, vitreous humor, choroid-retina, and optic nerve were compared following instillation of a single drop of 0.5% ophthalmic solutions into albino rabbit eyes. Tissue drug and metabolite concentrations were measured by liquid chromatography-mass spectrometry. Dihydrobunolol (DHB) is an equipotent metabolite of levobunolol. In the anterior segment of the eye, levobunolol plus DHB concentrations were higher than timolol concentrations in aqueous humor and were comparable to those of timolol in iris-ciliary body. However, in the choroid-retina and optic nerve, timolol concentrations were greater than those of levobunolol plus DHB. Overall, the study demonstrates comparable concentrations of levobunolol and timolol in the anterior section of the eye. The low availability of levobunolol in the posterior segment as compared to timolol may be a key advantage for levobunolol in producing less adverse effect on blood flow in the choroid-retina and optic nerve.

Absorption↗
PubMed1996

Basis for dosing time-dependent changes in the ocular and systemic absorption of topically applied timolol.

The objective of the present study was to determine the basis for dosing time-dependent changes in the ocular and systemic absorption of topically applied timolol in pigmented rabbits. The gamma scintigraphic technique was used to monitor the changes in precorneal solution retention following instillation. Changes in timolol concentration in the plasma over 120 min and in various anterior segment eye tissues at 30 min following the topical instillation of 25 microliters of 0.65% timolol maleate solutions at various dosing times were monitored using reversed phase HPLC. Corneal and conjunctival permeability at various dosing times was evaluated in the modified Ussing chamber. The results indicated that precorneal solution drainage was slowest at noon. Suppressing tear production by anesthesia led to an increase in ocular timolol absorption at 6 a.m. but not at other dosing times, in spite of the lowest corneal permeability then. There was no statistically significant dosing time influence on systemic timolol absorption following nasal or conjunctival dosing. In conclusion, possible diurnal changes in precorneal solution clearance may be the main factor underlying the diurnal changes in ocular as well as systemic timolol absorption in rabbits. In addition, diurnal changes in corneal permeability may also contribute to diurnal changes in ocular timolol absorption.

Absorption↗
PubMed2005

Physicochemical properties and in vivo assessment of timolol-loaded poly(D,L-lactide-co-glycolide) films for long-term intraocular pressure lowering effects.

Timolol-loaded poly(D,L-lactide-co-glycolide; PLGA) films were prepared for achieving the long-term intraocular pressure (IOP) lowering effect on glaucoma treatment. The physicochemical properties and in vivo effects of films were determined and characterize the delivery system. PLGA, span 20, propylene glycol (PG), and timolol base were dissolved in dichloromethane (DCM) and kept in a stainless mold; timolol films were prepared after the evaporation of DCM. Timolol disc-shape film preparation (TDF), containing 1 mg of timolol in 0.37 cm(2) area, was fabricated by using a trephine and placed onto the cul de sac of alpha-chymotrypsin-induced ocular hypertension rabbits for assessing the IOP lowering effect. The prepared films characterized a Young's modulus ranged from 1.13 to approximately 2.49 MPa, and related to the content percentages of PLGA, PG, and the residual DCM. The timolol film could maintain drug release for 1 week. Following a single-dose application in ocular hypertension rabbits, the prepared TDF could achieve a long-term IOP lowering effect and maintain the IOP change (in comparison with baseline) of approximately 7 mmHg within 1 week. The aqueous humor levels of timolol were low within a range of 0.8 to approximately 0.24 microg/mL for the initial 24 h and less than 0.15 microg/mL for 4-7 days. The investigated film formulation might be potentially developed for the application of long-term ocular delivery systems.

Adrenergic beta-Antagonists↗
PubMed2005

Comparison of the efficacy and safety of dorzolamide 2% when added to brimonidine 0.2% or timolol maleate 0.5% in patients with primary open-angle glaucoma.

OBJECTIVE: To determine the ocular hypotensive efficacy and safety of dorzolamide when added to brimonidine or timolol in patients with uncontrolled primary open-angle glaucoma (POAG). PATIENTS AND METHODS: This is a 1-year prospective open-label clinical trial of 48 consecutive POAG patients with inadequate intraocular pressure (IOP) control while using brimonidine 0.2% (23 patients) and timolol 0.5% (25 patients), 2 times daily. Patients were assigned to receive dorzolamide 2% as adjunctive therapy, added 3 times daily to brimonidine or timolol. IOP was measured on week 2, and months 3, 6, 9, and 12. RESULTS: A significant reduction in IOP from the baseline was observed after dorzolamide use in both groups at visits during that year (P < 0.001). Overall, mean IOP reduction was 5.6 +/- 1.9 mmHg with the brimonidine-dorzolamide combination, and 6.8 +/- 1.7 mmHg with timolol-dorzolamide after 1 year of treatment; the difference was significant (P = 0.029). No statistical differences existed between the groups for adverse events (P < 0.05). CONCLUSION: The addition of dorzolamide to brimonidine or timolol has significant IOP-lowering efficacy during 1 year in patients with POAG whose IOPs were inadequately controlled with brimonidine or timolol alone. The IOP-lowering effect of the timolol-dorzolamide combination at 1 year was more pronounced than brimonidine-dorzolamide. Both combinations were well-tolerated by the patients.

Adult↗
PubMedDate not supplied

Initial evaluation of transdermal timolol: serum concentrations and beta-blockade.

The serum concentrations and beta-blockade after dermal application of timolol ointment were evaluated in six healthy men (21-31 years old; 74-82 kg). Two patches (25 cm2) containing placebo and either 30 (n = 2) or 60 mg (n = 4) timolol base were randomly applied to the chest for 30 h. Serial serum concentrations of timolol were measured by a radioligand receptor assay. Bicycle ergometry, at a predetermined workload, was performed before and at 3, 8, 24, and 48 h after patch application; mean +/- SD heart rates (beats/min) at these times were 167 +/- 2, 158 +/- 7, 125 +/- 7, 120 +/- 5, and 150 +/- 5 (last 3 values: p less than 0.05 from pretreatment), and beta-blockade was evident in all subjects. Measurable serum concentrations in the therapeutic range were achieved in all subjects. The change in exercise-induced heart rate (y) was closely related to log timolol serum concentration (x) (y = -36 X - 5.3; r = -0.92; p less than 0.001). Based on the amount of timolol in the residual ointment, 50-60% of the original timolol dosage was delivered from the patch. Skin irritation under the patch compared with placebo was minimal. Further studies are warranted to assess the potential clinical utility of transdermal timolol.

Adult↗
PubMed1998

A comparison of the effects of betaxolol, timolol, and pilocarpine on visual function in patients with open-angle glaucoma.

PURPOSE: The author compares the effect of betaxolol, timolol, and pilocarpine on visual functions in patients with glaucoma. METHODS: Sixty-eight patients with early glaucoma were randomly allocated to betaxolol, timolol, or pilocarpine treatment and their visual fields, motion detection, and contrast sensitivity were studied over a 24-month period. A subset of the betaxolol and timolol group were also followed with short-wave automated perimetry. One eye of each patient was used in the analysis. RESULTS: All three drugs reduced pressure effectively. Pilocarpine and timolol were not significantly different from each other and both produced a more marked pressure reduction than betaxolol. There were no significant differences between the drugs on the visual fields, contrast sensitivity, or motion detection. Betaxolol appeared to have a better impact on the blue-yellow sensitivity of the upper nasal and upper temporal visual field quadrants than timolol. CONCLUSIONS: In spite of a greater pressure reduction, timolol did not have a more favorable effect on visual function. In the short-wave automated perimetry, the betaxolol did marginally better than timolol. The apparent dissociation between pressure reduction and protection of visual function deserves further study.

Adrenergic beta-Antagonists↗
PubMed2001

Comparison of topical travoprost eye drops given once daily and timolol 0.5% given twice daily in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: This 9-month study compared the intraocular pressure (IOP)-lowering efficacy and safety of once-daily travoprost ophthalmic solutions (0.0015% and 0.004%) with twice-daily timolol 0.5%. PATIENTS AND METHODS: This study was conducted using a double-masked, randomized, parallel-group design; adult patients with open-angle glaucoma or ocular hypertension (IOP between 24 and 36 mm Hg, inclusive at 9 am and between 21 and 36 mm Hg, inclusive, at 11 am and 4 pm on two eligibility visits after an appropriate washout of previous treatments). In both eyes, the travoprost vehicle (placebo) was instilled at 9 am and travoprost (0.0015% or 0.004%) was instilled at 9 pm, or timolol 0.5% was instilled at both times. The primary efficacy variable was mean IOP measured at 9 am, 11 am, and 4 pm at baseline and follow-up visits. RESULTS: Five hundred seventy-three patients were randomized to the study treatments. Mean IOP, which was combined across study visits, was lower with travoprost 0.004% than with timolol 0.5% at 9 am (P = 0.0246), 11 am (P = 0.0039), and 4 pm (P = 0.0004). Intraocular pressure was lower with travoprost 0.004% than with travoprost 0.0015% at 11 am (P = 0.0314), the time of peak drug activity. Mean IOP was consistently lower with travoprost 0.0015% than with timolol 0.5%. Mean IOP reductions from baseline were significantly (P less than equal 0.0001) greater with travoprost 0.004% (8.0-8.9 mm Hg) than with timolol 0.5% (6.3-7.9 mm Hg). The most frequent related adverse events were hyperemia, pruritus, discomfort, pain, and iris pigmentation changes. The local tolerance was better in the timolol group compared with patients receiving travoprost. There were no serious unexpected treatment-related adverse events in any group. CONCLUSIONS: Travoprost 0.004% reduced diurnal mean intraocular pressure significantly more than timolol 0.5%. Both concentrations of travoprost were well tolerated and safe for use in patients with open-angle glaucoma or ocular hypertension.

Administration, Topical↗
PubMed2003

Pooled-data analysis of three randomized, double-masked, six-month studies comparing intraocular pressure-reducing effects of latanoprost and timolol in patients with ocular hypertension.

PURPOSE: To assess retrospectively the intraocular pressure (IOP)-reducing effect of latanoprost compared with timolol in the subset of patients with ocular hypertension (OH). METHODS: Three randomized, double-masked, multicenter, parallel group, 6-month studies conducted in the United States, United Kingdom, and Scandinavia compared the efficacy and safety of latanoprost and timolol. The present study represents an analysis of the pooled data for the subset of OH patients. Intent-to-treat analyses were based on all randomized OH patients. RESULTS: Of the 441 patients with OH, 247 were treated with latanoprost and 194 were treated with timolol. Baseline mean diurnal IOP levels were 24.4 +/- 0.2 mm Hg (mean +/- standard error of the mean) in the latanoprost group and 24.2 +/- 0.2 mm Hg in the timolol group. Overall, latanoprost lowered mean diurnal IOP by 1.1 +/- 0.2 mm Hg (95% CI: 1.6 to 0.7 mm Hg, P < 0.001) more than timolol. The difference in IOP-lowering ability between the two drugs was not shown to be related to patient sex, age, race, presence or absence of previous treatment of OH, time elapsed since ocular diagnosis, or family history of glaucoma/OH. Percentage reductions from baseline in diurnal IOP levels of at least 20% were achieved by 83% of patients treated with latanoprost versus 62% of those receiving timolol. CONCLUSION: Latanoprost provides superior IOP reduction compared with timolol in patients with OH.

Antihypertensive Agents↗
PubMed2003

Rate of response to latanoprost or timolol in patients with ocular hypertension or glaucoma.

PURPOSE: This study determined the rate of response to latanoprost compared with timolol in patients with glaucoma or ocular hypertension, whether some patients convert from non-responders to responders after more prolonged therapy, and whether this conversion represents a delayed response or random fluctuation. METHODS: In a previously described, multicenter, randomized, double-masked, parallel group study, patients received either 0.005% latanoprost once daily (n = 128) or 0.5% timolol twice daily (n = 140) for 6 months. Intraocular pressure (IOP) was assessed at baseline and at 0.5, 1.5, 3, 4.5, and 6 months of treatment at 8 am on all visits, and also at noon and 4 pm at baseline and 6 months. Rate of response based on diurnal measurement at 6 months compared with baseline was assessed using several criteria for response. Eyes with an IOP reduction of less than 15% compared with baseline at 8 am arbitrarily were classified as non-responders at each of the 5 visits during treatment. Consistency of non-responder classifications for individual eyes was assessed. RESULTS: Mean IOP reduction was greater (P < 0.001) in latanoprost-versus timolol-treated patients throughout the course of therapy. A greater rate of response occurred in patients treated with latanoprost, and differences in response rates between the 2 drugs increased as the definitions of response became more stringent. A greater percentage of non-responders at any single visit were classified as responders at all other visits with latanoprost in comparison with timolol. CONCLUSIONS: Latanoprost produces a greater rate of response compared with timolol. A higher percentage of non-responders to latanoprost compared with timolol on any individual visit are responders on all other visits. Likewise, a higher proportion of patients who do not initially respond will become responders with continued treatment with latanoprost compared with timolol.

Antihypertensive Agents↗
PubMed2006

Travoprost compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension: meta-analysis of randomized controlled trials.

BACKGROUND: It is still uncertain whether travoprost has comparable or better efficacy compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension. The authors performed a meta-analysis of randomized controlled trials to evaluate the incidence of reported side-effects and intraocular pressure (IOP)-lowering effect of travoprost versus other prostaglandin analogues (latanaprost, bimatoprost, unoprostone) or timolol. METHODS: Systematic literature retrieval was conducted in Pubmed, EMBASE, Chinese Bio-medicine Database and Cochrane Controlled Trials Register to identify the potentially relevant randomized controlled trials. The statistical analysis was performed by RevMan 4.1 software that was provided by the Cochrane Collaboration. The outcome measures were the incidence of reported side-effects (hyperaemia, iris pigmentation, eyelash changes) and mean IOP pooled over treatment visits. RESULTS: In total, 12 articles involving 3048 patients with open-angle glaucoma or ocular hypertension were included in this meta-analysis. The combined results showed that travoprost 0.004% was more effective than timolol or travoprost 0.0015% in lowering IOP, but not more effective than bimatoprost or latanoprost. Travoprost 0.004% caused a higher percentage of hyperaemia than timolol, latanoprost, or travoprost 0.0015%. There was an increased incidence of pigmentation with travoprost than timolol. Travoprost 0.004% caused a higher percentage of eyelash changes than timolol, latanoprost, or travoprost 0.0015%. CONCLUSION: According to data available, travoprost is more effective than timolol in lowering IOP in patients with open-angle glaucoma or ocular hypertension. Compared with other prostaglandin analogues, travoprost appears to be equivalent to bimatoprost and latanoprost. Although a limited number of local side-effects were reported, no serious treatment-related side-effects were reported.

Aged↗
PubMed1984

The effects of timolol on arrhythmias and prostanoid release during canine myocardial ischaemia and reperfusion.

Timolol (50 micrograms kg-1), administered intravenously to chloralose-anaesthetized open-chest greyhounds 30 min prior to occlusion of the left anterior descending coronary artery, reduced heart rate and mean arterial blood pressure. This dose caused a 20 fold increase in the dose of isoprenaline required to increase heart rate by 25 beats min-1. During the first 30 min of myocardial ischaemia the number of extrasystoles in the timolol-treated dogs (327 +/- 179) was less than in the control group (888 +/- 168) and none of the dogs that received timolol fibrillated. The haemodynamic changes induced by coronary artery occlusion (decreased cardiac output and stroke volume, increased peripheral vascular resistance) were similar in both control and timolol-treated dogs as were the increases in PCO2 and decreases in PO2 and pH in blood draining from the ischaemic myocardium. Timolol did not alter the release during myocardial ischaemia, of either thromboxane B2 or prostacyclin (measured as 6-keto PGF1 alpha). Reperfusion-induced ventricular fibrillation occurred in 7 out of 8 control dogs and in 5 out of 10 timolol-treated dogs. The overall survival following occlusion and reperfusion was improved by 10% to 50% by timolol.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Timolol vs propranolol vs placebo in common migraine prophylaxis: a double-blind multicenter trial.

Common migraine sufferers (25 males, 71 females) with a history of 2-6 attacks per month participated in a 4-centre trial comparing the prophylactic effect of timolol (10 mg b.i.d.) and propranolol (80 mg b.i.d.) to placebo. After a pretreatment period of 4 weeks they entered a double-blind 3-way cross-over trial with 3 treatment periods of 12 weeks each. 83 patients received all 3 treatments. The mean frequency of attacks per 28 days was 3.35 on timolol, 3.69 on propranolol and 4.83 on placebo. Mean severity of attacks (0-3) was 1.75 on timolol, 1.83 on propranolol, and 1.93 on placebo. Mean duration of attacks was 7.41 h on timolol, 7.38 on propranolol and 7.95 on placebo. The headache index (frequency times severity) was 5.71 on timolol, 6.66 on propranolol and 9.03 on placebo (P less than 0.05, P less than 0.01 compared to placebo). The difference between propranolol and timolol was non-significant: frequency of attacks 0.34 (95% confidence limits - 0.26; 0.89). Headache index 0.95 propranolol and 23 patients on placebo experienced side effects (P less than 0.05). It is concluded that timolol and propranolol are equally effective in the used doses (1:8) for common migraine prophylaxis.

Adolescent↗
PubMed1989

Long-term evaluation of timolol.

Maintenance effect of the topical beta-blocker timolol on intraocular pressure (IOP) was investigated for a mean follow-up of 31.6 months in a group of 155 patients (275 eyes) with glaucoma or ocular hypertension. The mean IOP-value was calculated from 3 readings of the daytime IOP curve, and the mean eye pressure of the right and left eye in the respective individual was used. The medical therapy was carried out with our ranking order of drugs of choice: timolol, timolol combined with adjunctive drug therapy, laser trabeculoplasty and/or filtering surgery. Intraocular pressure was controlled with timolol alone in 98 of 155 patients (63.2%, Group 1). In 36 patients, timolol plus adjunctive medication was required to control IOP (23.2%, Group 2). Twenty-one (13.6%, Group 3) required either laser trabeculoplasty or filtering surgery in addition to timolol. Sufficient IOP-lowering effect was more frequently maintained in patients with ocular hypertension than those with glaucoma simplex or capsular glaucoma. Failures in timolol treatment occurred mostly within 6 months from the start of the therapy and correlated well with higher initial IOP. Transient adverse effects were observed in 11.2% of cases. In three cases (1.9%) local and systemic side effects were serious enough to require discontinuation of the drug therapy. One patient (0.7%) was a non-responder and was withdrawn from the study for that reason. Sixteen patients (10.3%) were lost to follow-up during the 4 year study.

Adult↗
PubMed2005

Topically administered timolol and dorzolamide reduce intraocular pressure and protect retinal ganglion cells in a rat experimental glaucoma model.

AIMS: This study sought to elucidate the effects of timolol and dorzolamide on intraocular pressure (IOP) and retinal ganglion cell (RGC) death in an experimental model of glaucoma in rat. METHODS: Mild elevation of IOP was induced in rats by intracameral injection of India ink and subsequent laser trabecular photocoagulation. IOP was measured before the surgical procedures and weekly thereafter. Timolol (0.5%), timolol XE (0.5%), dorzolamide (1%), and artificial tears (vehicle) were topically applied daily. Retinal sections were prepared for histology to determine RGC number. RESULTS: Timolol, timolol XE, and dorzolamide induced a significant reduction in IOP (p<0.05) and counteracted the reduction in RGC number that occurred in vehicle treated glaucomatous eyes (p<0.05). The coefficient of correlation between RGC number and IOP was significant in the dorzolamide treated group (r = -0.908, p<0.005), but not in other groups (p>0.05). CONCLUSIONS: Both timolol formulation and dorzolamide reduced IOP and protected RGCs in a rat model of experimental glaucoma. It cannot be ruled out that timolol might protect RGCs by additional mechanisms other than simply lowering of IOP.

Animals↗
PubMed1994

The contralateral reduction of intraocular pressure by timolol.

Administration of timolol to one eye is associated with a decrease in intraocular pressure in both eyes. To further investigate this effect the contralateral decrease in intraocular pressure was measured in a three arm crossover study using a 0.1 mg dose of timolol given topically to an eye, a 0.1 mg dose of timolol given lingually, and a placebo given topically. Two hours after topical timolol administration the mean intraocular pressure reduction in the fellow eye was 3.1 mm Hg compared with baseline (p = 0.0007). Two hours after lingual timolol administration the mean intraocular pressure reduction was 3.9 mm Hg compared with baseline (p = 0.0004). Two hours after topical administration of placebo the mean intraocular pressure reduction in the fellow eye was only 0.33 mm Hg (p = 0.6). These findings suggest the contralateral reduction in intraocular pressure from timolol is caused by systemic absorption. The significant intraocular pressure reduction obtained from lingual timolol raises the possibility that this route of drug administration may be useful in selected patients who cannot use eye drops.

Administration, Topical↗
PubMed1994

Additive effect of latanoprost, a prostaglandin F2 alpha analogue, and timolol in patients with elevated intraocular pressure.

A randomised observer masked clinical study was conducted to assess the additive effect of latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinorprostaglandin F2 alpha-isopropylester) to timolol maleate in patients with elevated intraocular pressure (IOP). Patients were randomly assigned to two treatment groups. One group (n = 10) received timolol, the other group (n = 9) received latanoprost twice daily for 1 week. After 1 week all patients received both timolol and latanoprost. Eyes treated with timolol (mean diurnal IOP (SD) day 0, 24.2 (2.8) mm Hg) and latanoprost (mean diurnal IOP day 0, 28.5 (5.6) mm Hg) showed an IOP reduction of 5.9 (2.3) mm Hg (24%) and 8.9 (2.5) mm Hg (31%), respectively after the first week. Adding latanoprost to the eyes treated with timolol as well as timolol to the eyes receiving latanoprost gave a further reduction of 2.6 (1.1) mm Hg (13%) and 2.6 (2.2) mm Hg (14%), respectively. Only mild transient hyperaemia was observed in patients receiving latanoprost. The results indicate that latanoprost and timolol can be combined successfully and that complete or almost complete additivity is reached even at pressure levels below 20 mm Hg.

Adult↗