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At least 397 records · Page 22Linked to original sources

PubMed2000

Effect of single- and multiple-dose 0.5% timolol maleate on intraocular pressure and pupil size in female horses.

OBJECTIVE: To determine the effect of single and multiple-dose 0.5% timolol maleate on intraocular pressure (IOP) and pupil size between 8 AM and 8 PM. Animals Nine female horses with normotensive eyes. Procedure IOP, horizontal and vertical pupil size were measured on a single day, between 8 AM and 8 PM at hours 0, 0.5, 1, 2, 4, 6, 8, 10, and 12. A single dose of 0.5% timolol maleate was applied to both eyes immediately after the first measurement at 8 AM. IOP and pupil size were measured at 8 AM and 4 PM in a 5-day experiment of twice-daily application of 0.5% timolol maleate. RESULTS: A significant decrease in IOP from 24.9 +/- 4.2 mmHg prior to application of timolol maleate to 20.7 +/- 3.1 mmHg (4.2 mmHg = 17%) was observed 8 h after single-dose application. A significant decrease in horizontal pupil size (2.0 mm = 11%) was present 6 h after single-dose application. In the multiple-dose experiment, a significant decrease in IOP was present on days 4 and 5 as compared to IOP measured prior to application of timolol maleate. A significant decrease in horizontal and vertical pupil size was present throughout the 5-day study as compared to the values obtained prior to treatment. CONCLUSIONS: 0.5% timolol maleate significantly decreased IOP and pupil size in normo-tensive eyes of this group of female horses in both single and multiple twice daily applications.

Journal Article↗

PubMed1976

Suppression of renin release by timolol.

The beta-adrenergic blocking agent, timolol, administered to resting rabbits as an i.v. bolus (0.125 mg/kg) sustained by a 2-hr infusion at 0.0625 mg/kg/hr, caused significant depression of plasma renin activity (PRA) to 49% of the control level. Significant correlations emerged between the fall in mean blood pressure and changes in both heart rate and PRA. Timolol also antagonized isoprenaline-induced renin release. In anaesthetized normal rats, timolol (0.2 mg/kg i.p.) suppressed mean plasma renin concentration (PRC) to 16% of the pre-treatment value. Furthermore, the mean PRC of normal rats, bled immediately after decapitation, to avoid stimulating renin secretion, was reduced by 55% one hr after i.p. injection of timolol. The potency of timolol in this respect was 8 times that of dl-propranolol. Thus, in rabbits and rats, timolol effectively depresses both basal and stimulated plasma renin levels.

Adrenergic beta-Antagonists↗

PubMed1998

A double-masked, randomized, 1-year study comparing the corneal effects of dorzolamide, timolol, and betaxolol. Dorzolamide Corneal Effects Study Group.

OBJECTIVE: To compare the long-term effects of dorzolamide hydrochloride (Trusopt, Merck and Co Inc, White-house Station, NJ), timolol maleate, and betaxolol hydrochloride on corneal endothelial cell density and corneal thickness. METHODS: This 1-year multicenter study was conducted in 298 patients with ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density greater than 1500 cells/mm2 and central corneal thickness less than 0.68 mm in each eye. Patients were randomized to 0.5% betaxolol twice daily, 0.5% timolol twice daily, or 2.0% dorzolamide 3 times daily. Specular microscopy and ultrasonic pachymetry of the central cornea was performed at baseline and 6 and 12 months following institution of therapy. Endothelial cell densities were determined by a single masked observer. RESULTS: The mean percent changes from baseline for both outcome measures were similar in all 3 treatment groups at both 6 and 12 months. After 1 year of treatment, the mean percent loss in endothelial cell density from baseline was 3.6%, 4.5%, and 4.2% for the dorzolamide, timolol, and betaxolol groups, respectively. The mean percent change from baseline for corneal thickness was 0.47%, -0.25%, and 0.39% for the dorzolamide, timolol, and betaxolol groups, respectively. CONCLUSIONS: Dorzolamide is equivalent to timolol and betaxolol in terms of the change in central endothelial cell density and thickness after 1 year of therapy. All 3 treatments exhibit good long-term corneal tolerability in patients with normal corneas at baseline.

Adrenergic beta-Antagonists↗

PubMed2001

Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy, and safety evaluation of a novel compound for glaucoma management.

OBJECTIVE: To compare the safety and efficacy of the ocular hypotensive lipid AGN 192024 (Lumigan) with those of timolol. METHODS: A 30-day, randomized, investigator-masked, clinical trial involving 100 patients with elevated intraocular pressure (IOP). Study medications were instilled topically. Doses of 0.003%, 0.01%, or 0.03% AGN 192024 were given once daily for 3 weeks then twice daily for 1 week, and vehicle control or 0.5% timolol was given twice daily for 4 weeks. Mean change in IOP from baseline was the primary efficacy variable. Safety parameters included adverse events, hyperemia grading, laser flare meter analysis, heart rate, and blood pressure. RESULTS: Timolol and all 3 concentrations of AGN 192024 lowered IOP from baseline (P < .001). A dosage of 0.03% AGN 192024 once daily lowered IOP significantly more than timolol (P < or = .02) at every study visit except day 21 (P = .053) and provided better diurnal IOP control. Twice-daily dosing of AGN 192024 provided no clinically significant benefit over once-daily dosing. All treatment regimens were safe and well tolerated, with no clinically significant effects on heart rate or blood pressure and no between-group differences in the incidence of adverse events. The only significant ocular safety finding with AGN 192024 was a dose-related mild increase in conjunctival hyperemia. CONCLUSIONS: Of the 3 concentrations tested, 0.03% AGN 192024 once daily had the best therapeutic profile. AGN 192024 was safe and well tolerated, and it provided superior ocular hypotensive efficacy and diurnal IOP control compared with timolol in patients with ocular hypertension and glaucoma.

Adult↗

PubMed2002

Latanoprost and timolol combination therapy vs monotherapy: one-year randomized trial.

OBJECTIVE: To compare the efficacy and safety of a fixed combination of 0.005% latanoprost and 0.5% timolol maleate administered once daily vs monotherapy with either 0.005% latanoprost once daily or 0.5% timolol twice daily. METHODS: Patients with either primary or secondary open-angle glaucoma or ocular hypertension participated in a 6-month, randomized, double-masked, multicenter study with 3 parallel treatment groups. The double-masked period was preceded by a 2- to 4-week "run-in" treatment with timolol. Subjects could receive fixed combination therapy during a 6-month open-label extension. MAIN OUTCOME MEASURE: The difference between groups in mean diurnal intraocular pressure reduction in study eye(s) from baseline through 6 months of treatment. RESULTS: Overall, 418 patients were enrolled in the study; 332 completed the open-label phase. Diurnal intraocular pressure levels were similar at baseline, but at week 26, they were 19.9 +/- 3.4 mm Hg in the fixed combination therapy group, 20.8 +/- 4.6 mm Hg in latanoprost-treated patients, and 23.4 +/- 5.4 mm Hg in timolol-treated patients (data are given as mean +/- SD). The mean change from baseline was greater among patients receiving fixed combination therapy compared with each monotherapy group (P<.01). Fixed combination therapy effectively lowered intraocular pressure levels for up to 1 year. All treatments were well tolerated. CONCLUSION: The combination of 0.005% latanoprost and 0.5% timolol administered once daily is effective and well tolerated for up to 12 months.

Adult↗

PubMed2004

Crossover comparison of timolol and latanoprost in chronic primary angle-closure glaucoma.

OBJECTIVE: To compare latanoprost and timolol maleate as primary therapy in 60 eyes with chronic primary angle-closure glaucoma after a laser iridotomy. METHODS: We performed a prospective, randomized, crossover study of 60 eyes of 30 patients with chronic primary angle-closure glaucoma after laser iridotomy. Patients were randomized to 2 groups: those taking latanoprost once daily or those taking timolol twice daily. Three months after treatment with the first drug, the second drug was substituted. The circadian rhythm of intraocular pressure (IOP) was recorded before the start of therapy, at 3 months, and at 7 months. The fourth month was the washout period for the first drug. RESULTS: The mean baseline IOP was 23.5 +/- 2.1 mm Hg, which decreased by 8.2 +/- 2.0 mm Hg with latanoprost (P<.001) and by 6.1 +/- 1.7 mm Hg with timolol (P =.01). The decrease in IOP was greater for patients taking latanoprost (P<.001). Latanoprost was significantly more effective in eyes having morning and afternoon peaks of IOP. A total of 43 eyes (72%) of patients taking latanoprost and 26 (43%) on timolol achieved a reduction of more than 30% from baseline IOP. CONCLUSION: There were greater mean and peak IOP reductions achieved with 0.005% latanoprost once daily compared with 0.5% timolol twice daily.

Aged↗

PubMed1980

Penetration of timolol into the rabbit eye. Measurements after ocular instillation and intravenous injection.

The distribution of radioactivity in 15 ocular and extraocular tissues or fluids of the rabbit after ocular instillation and intravenous injection of 100 microL of 14C-labeled timolol solution (1.5%) was studied by liquid scintillation counting (LSC). The drug was distributed rapidly among the tissues examined after both routes of administration. Levels of radioactivity were considerably greater in ocular tissues after instillation as compared with intravenous injection, whereas in extraocular tissues the levels were similar after both routes of administration. Using the same experimental protocol, aqueous humor and serum levels of unchanged timolol were measured by gas liquid chromatography. Comparisons with LSC studies indicated that, following ocular instillation, only unchanged timolol was present in aqueous humor, whereas both timolol and metabolites were present in serum. After intravenous administration, timolol was rapidly metabolized and metabolites appeared in the serum and aqueous humor.

Administration, Topical↗

PubMed1981

Effects of timolol on bovine corneal endothelial cultures.

The chronic use of timolol (Timoptic) maleate to control glaucoma may produce cytotoxic complications in the cornea. We have therefore compared the relative toxic effects of the commercial ophthalmic preparation with that of the pure compound. Commercial vehicle, either with or without 16 mM timolol maleate, killed cultures within the first five minutes of exposure. Pure timolol maleate, however, caused rapid but reversible cellular contractions, and cells remained viable in it for over 24 hours. Dilution with culture medium reduced both the cytotoxicity and the speed of the contractions. Incubation in 1:100 dilutions of vehicle or commercial drug preparations or in 0.16 mM pure timolol maleate did not alter cellular morphology. The results indicate that while undiluted vehicle is toxic, timolol maleate is not.

Animals↗

PubMed1982

Additive effect of epinephrine to timolol therapy in primary open angle glaucoma.

Previous studies have suggested that the effect on intraocular pressure resulting from the combined use of timolol and epinephrine might be different when they are administered hours rather than minutes apart. Fourteen patients were randomly assigned to one of two treatment sequences in which 1% epinephrine borate was added either five minutes or three hours after 0.5% timolol maleate. Combined therapy was continued for two weeks, after which epinephrine administration was stopped for a two-week washout period. The patient groups were then crossed over to the other dosage interval. There was an initial enhancement of pressure reduction when epinephrine was added to timolol in both sequences. After crossover, epinephrine was significantly additive to timolol in reducing pressure only when administered three hours after timolol. This additive effect was still present after three months of combined therapy.

Adult↗

PubMed1982

Timolol and epinephrine: long-term evaluation of concurrent administration.

Thirty-two ocular hypertensive subjects were treated for 90 days with either 0.5% timolol maleate or 2% epinephrine hydrochloride twice daily to one eye and both drugs to the fellow eye. The ocular hypotensive effects of timolol and epinephrine were partially additive throughout the course of this study. On the 91st day, eyes treated with epinephrine had a 25.8% mean reduction of intraocular pressure from baseline, whereas their fellow eyes treated with epinephrine and timolol had a 33.9% reduction. Eyes treated with timolol had a 27.2% mean reduction of IOP, whereas fellow eyes treated with timolol and epinephrine had a 29% reduction. These results suggest that the majority of patients being treated with either drug are unlikely to have a substantial long-term reduction in IOP when the other drug is added to their therapeutic regimen.

Administration, Topical↗

PubMed1991

Effects of topical flurbiprofen on the intraocular pressure lowering effects of apraclonidine and timolol.

We performed a prospective study that evaluated whether pretreatment with topical flurbiprofen alters the intraocular pressure (IOP) lowering effects of either topical 1% apraclonidine hydrochloride or 0.5% timolol maleate. Eighteen normal volunteers participated in this six-armed, randomized, double-masked, crossover study. All subjects received the first study medication, either bilateral 0.3% flurbiprofen or placebo (its vehicle), every 30 minutes for four applications. They next received the second study medication: either 0.5% timolol maleate (Timoptic), 1% apraclonidine hydrochloride, or placebo in both eyes. We measured IOP before the instillation of the first study medication and the second study medication (baseline), and then at 1, 3, and 6 hours later. All subjects underwent all six treatment arms. Flurbiprofen alone had no effect on IOP. Maximum IOP lowering occurred between 3 and 6 hours after timolol and apraclonidine administration. There was no difference in IOP lowering between timolol- and apraclonidine-treated eyes. Pretreatment with flurbiprofen did not affect the IOP lowering that was obtained with timolol or apraclonidine administration.

Administration, Topical↗

PubMed1995

A double-masked, randomized 1-year study comparing dorzolamide (Trusopt), timolol, and betaxolol. International Dorzolamide Study Group.

OBJECTIVE: To investigate the safety profile and efficacy of 2.0% dorzolamide hydrochloride, when administered three times daily for up to 1 year, compared with that of 0.5% timolol maleate and 0.5% betaxolol hydrochloride, each administered twice daily. In addition, the effect of adding dorzolamide to the regimen of patients with inadequate ocular hypotensive efficacy while they were receiving one of the two beta-adrenoceptor antagonists and the effect of adding timolol to the regimen of patients receiving dorzolamide were also evaluated. DESIGN: A double-masked, randomized, parallel comparison. SETTING: Multinational study at 34 international sites. PATIENTS: Five hundred twenty-three patients with open-angle glaucoma or ocular hypertension, 17 to 85 years of age. Patients currently using ocular hypotensive medications were required to undergo a washout. INTERVENTION: Two percent dorzolamide three times a day, 0.5% timolol (Timoptic, Merck, Whitehouse Station, NJ) twice daily, and 0.5% betaxolol solution (Betoptic, Alcon, Fort Worth, Tex) twice daily. RESULTS: At 1 year, the mean percent reduction in intraocular pressure at peak of 2% dorzolamide, 0.5% timolol, and 0.5% betaxolol was approximately 23%, 25%, and 21%, respectively. At afternoon trough, the mean percent reduction in intraocular pressure was 17%, 20%, and 15% for dorzolamide, timolol, and betaxolol, respectively. CONCLUSIONS: The ocular hypotensive efficacy of 2.0% dorzolamide, given three times a day, is comparable with that of 0.5% betaxolol, given twice daily, for up to 1 year. In addition, long-term use of dorzolamide was not associated with clinically meaningful electrolyte disturbances or systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors.

Administration, Topical↗

PubMed1997

Comparison of dorzolamide and timolol as suppressors of aqueous humor flow in humans.

OBJECTIVES: To measure the effectiveness of topical 2% dorzolamide hydrochloride (Trusopt, Merck & Co Inc, Whitehouse Station, NJ) as a suppressor of aqueous humor flow in the human eye as compared with the effectiveness of 0.5% timolol maleate (Timoptic, Merck & Co Inc) and to measure the additivity of the 2 drugs. DESIGN: A randomized, double-masked, placebo-controlled study of 40 human subjects was carried out in 2 academic centers (Mayo Clinic, Rochester, Minn, and University of Uppsala, Uppsala, Sweden). The rate of aqueous flow was measured from 8 AM to 4 PM by means of fluorophotometry after administration of doses of each drug singly and both drugs together. RESULTS: Dorzolamide reduced aqueous flow from 3.07 +/- 0.63 microL/min (mean +/- SD) to 2.53 +/- 0.60 microL/min, a reduction of 18% (P < .001). Timolol reduced aqueous flow from the same beginning rate to 1.64 +/- 0.35 microL/min, a reduction of 47% (P < .001). The inhibitory effect of timolol was 2.6 times the inhibitory effect of dorzolamide (P < .001). The 2 drugs were almost completely additive, and together reduced the flow to 1.37 +/- 0.33 microL/min, a reduction of 55%. Consistent effects were observed on intraocular pressure. CONCLUSIONS: Timolol is more effective than dorzolamide as a suppressor of aqueous humor flow in the normal human eye. Timolol and dorzolamide are additive in their effects, both on aqueous flow and intraocular pressure.

Adrenergic beta-Antagonists↗

PubMed1979

Serum potassium and uric acid changes during treatment with timolol alone and in combination with a diuretic.

Timolol, 10 to 40 mg daily, given to 103 patients with uncomplicated arterial hypertension induced significant increments of serum potassium at all dose levels (p less than 0.05). The magnitude of the increments was dependent on daily timolol dosage. When hydrochlorothiazide and amiloride were added, serum potassium decreased (p less than 0.001), but a major determinant of the magnitude of the decrease was the dosage change of the timolol. Serum uric acid was influenced in a paradoxical way during timolol monotherapy; there was a rise in all 3 dosage groups (p less than 0.02) but the lowest group showed the largest increase and vice versa. On addition of hydrochlorothiazide and amiloride, there was a further increase in serum uric acid, the magnitude of which depended on the concomitant reduction in the dose of timolol, with reductions in dose causing a larger rise in serum uric acid and increments, a smaller rise. The increments of serum uric acid were greater in females than in males during both treatment periods. The results indicate that beta blockers induce dose-dependent rises in serum potassium and may counteract undesirable effects of diuretics on serum potassium. Beta blockers seem to have a paradoxical effect on serum uric acid and may aggravate the hyperuricemia induced by diuretics.

Amiloride↗

PubMed1988

The effect of timolol given five minutes after coronary occlusion on plasma catecholamines.

The reported study determined whether timolol would afford a protective effect by preventing the coronary occlusion-induced arrhythmias associated with the increase in plasma norepinephrine (NE) and epinephrine (E). Ten anesthetized cats received saline or timolol (5 mg/kg, IV) five minutes after coronary occlusion of the left anterior descending coronary artery 10 to 14 mm below its origin. Coronary occlusion produced arrhythmia in three of the cats that received saline and in four of the cats that received timolol. Three of the saline-treated cats died in cardiogenic shock; two were sacrificed six hours postocclusion. Four of the timolol-treated cats died in congestive heart failure postcoronary occlusion. There was a gradual increase in NE (P greater than .05) and E (P less than .05) in both groups after coronary occlusion. Death produced a significant increase in NE and E levels. Timolol did not modify the occurrence of arrhythmias and the associated increase in plasma NE and E that developed after coronary occlusion and at death.

Animals↗

PubMedDate not supplied

Pharmacokinetics, mechanisms of action, indications, and adverse effects of timolol maleate, a nonselective beta-adrenoreceptor blocking agent.

Timolol, a nonselective beta-adrenoreceptor blocking agent without intrinsic sympathomimetic or membrane stabilizing activity, has been shown effective in the treatment of angina and hypertension. It is particularly useful in patients with stable angina pectoris and patients with mild to moderate hypertension. In both of these conditions, timolol appears to be comparable to propranolol. A recent study has suggested that timolol reduces mortality and reinfarction rate in patients who have recently had a myocardial infarction. When given topically timolol reduces intraocular pressure in patients with open-angle glaucoma; the drug may be used as the primary agent or as an adjunct to standard therapy. Careful selection of patients will reduce the frequency of adverse effects due to beta-receptor inhibition. Thus, timolol should not be used in patients who are predisposed to asthmatic bronchitis or cardiac failure, and it should be used with caution in patients with peripheral vascular disease or diabetes mellitus.

Arrhythmias, Cardiac↗

PubMed1990

Finite dose percutaneous drug absorption: theory and its application to in vitro timolol permeation.

The finite dose in vitro percutaneous absorption kinetics of timolol, a beta-blocker, was studied. The flux of timolol across excised human abdominal cadaver skin was measured over a period of 72 h following application of a 40-microns thickness patch containing 5, 10, or 20% (w/v) timolol free base. Amounts of timolol in the patch and skin were also determined at 6, 12, 24, 48, and 72 h after the application of the 20% (w/v) patch. The mean diffusion and partition parameters were estimated to be 0.018 h-1 and 125.9 microns, respectively, using a newly developed theory. Diffusion and partition parameters were estimated using the values for amounts of a drug eventually partitioning into the perfusing water, as well as two newly proposed conceptual parameter values, AUCAv and AUCAs which are the AUCs of drug amounts in vehicle and skin, respectively. The dose-dependent skin-timolol interaction is also discussed.

Administration, Topical↗

PubMed1991

Timolol release from matrices of monoesters of poly(vinyl methyl ether-maleic anhydride): effects of polymer molecular weight and a basic additive.

Alkyl monoesters of poly(vinyl methyl ether-maleic anhydride) (PVM-MA) are acidic bioerodible polymers that have been used in cosmetics and tablet film coatings. They may be suitable for topical controlled-release applications since the polymeric backbone is not cleaved to smaller fragments that could be absorbed into the systemic circulation. The dissolution of these polymers depends on the length of the alkyl ester chain of the polymer and on the pH on the polymer surface. We studied the effect of the molecular weight of the polymer on in vitro release of timolol from matrices of n-propyl, n-butyl, and n-hexyl monoesters of PVM-MA. The effect of a basic additive, disodium phosphate, on timolol release from the polymers was also evaluated. The rate of timolol release decreased with increasing length of the alkyl side chain in the polymer. Drug release from the n-propyl and n-butyl monoesters followed zero-order release kinetics, but that from the n-hexyl monoester followed square root-of-time release kinetics. The molecular weight of the polymer did not affect drug release from the matrices without disodium phosphate. With the basic additive, the rate of timolol release increased with increasing molecular weight from the matrices of n-propyl and n-butyl monoesters of PVM-MA, but had only a very small effect on drug release from the n-hexyl monoester. Release of timolol from the n-propyl and n-butyl monoesters was controlled by polymer dissolution and, thus, it was affected by the basic additive in the matrix. Diffusion-controlled drug release from the n-hexyl ester was not affected by disodium phosphate.

Delayed-Action Preparations↗