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PubMed2004

Persistency with latanoprost or timolol in primary open-angle glaucoma suspects.

PURPOSE: To evaluate persistency of pharmacotherapy in primary open-angle glaucoma suspects (glaucoma suspects) treated with latanoprost and timolol. DESIGN: Retrospective, cohort study using the Protocare Sciences managed care database; approximately 3 million members in commercial health maintenance organizations and preferred provider organizations and in Medicare risk plans. METHODS: Patients 20 years of age or older beginning therapy between January 1, 1997, and June 30, 2002, with latanoprost or timolol monotherapy were included. Patients must have been continuously enrolled and not undergone glaucoma surgery in the year preceding the index prescription fill and had glaucoma suspect diagnoses before and after the index date. Prescription refill records for all ocular hypotensives were extracted through June 30, 2002. The two outcome measures were (1) discontinuation of index drug, and (2) either discontinuation or change in index drug. Changing therapy was defined as switching to or adding another ocular hypotensive. Rates of discontinuation and discontinuation/change were compared using Cox regression models. RESULTS: In all, 1,474 patients met the inclusion criteria. Latanoprost was prescribed for 583 patients (40%) and timolol for 891 (60%). Compared with latanoprost, those treated with timolol were 39% more likely to discontinue and 27% more likely to discontinue/change therapy (P <.001 for both comparisons). At 12 months, 39% of patients receiving latanoprost and 25% of those treated with timolol had not discontinued therapy; no discontinuation or change in therapy was seen in 30% and 18%, respectively. CONCLUSIONS: Latanoprost-treated glaucoma suspects demonstrated significantly greater persistency than did patients treated with timolol. The reasons for this difference and its impact on intraocular pressure control and disease progression require further research.

Adult↗

PubMed2005

The influence of diclofenac ophthalmic solution on the intraocular pressure-lowering effect of topical 0.5% timolol and 0.005% latanoprost in primary open-angle glaucoma patients.

The aim of this randomized, prospective, masked clinical study has been to verify the influence of a non-steroidal anti-inflammatory drug ophthalmic solution on intraocular pressure reduction induced by 0.5% timolol and 0.005% latanoprost eyedrops in patients affected by primary open-angle glaucoma. Thirty-two glaucomatous patients, compensated with 0.5% timolol, were randomized into two study groups (A and B). Timolol was continued for the first 2 weeks in all subjects. On the 15th day, in both groups timolol was replaced by latanoprost, and this regimen lasted up to the end of the follow-up (8 weeks). At the beginning of the 2nd week of the study, group A additionally started a 5-week therapy with topical 0.1% diclofenac; during the same period, group B received placebo eyedrops with identical modalities. Intraocular pressure was recorded at 7-day intervals during the first 7 weeks and at the 10th week. Non-steroidal anti-inflammatory drug and placebo did not modify the effect of timolol on intraocular pressure. In both groups, latanoprost induced a significant decrease in intraocular pressure. Diclofenac-treated patients exhibited a marked fall in intraocular pressure (p<0.01), whereas in placebo-treated patients, this diminution was less noticeable (p<0.05). After diclofenac withdrawal, in group A intraocular pressure significantly increased (p<0.01), remaining approximately at the same level up to the end of the study. In group B, at the same checks no significant variations in intraocular pressure occurred. In primary open-angle glaucoma patients, diclofenac significantly enhances the hypotensive effect of latanoprost, without influence on timolol efficacy. Because non-steroidal anti-inflammatory drugs are widely employed in medical practice, supplementary ophthalmologic checks should be scheduled during the co-administration of these compounds and prostaglandin analogues.

Administration, Topical↗

PubMed2005

Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system.

In the present study chitosan (REVTMbio1) or Carbopol (REVTMbio2 and 3) coated niosomal timolol maleate (0.25%) formulations were prepared by reverse phase evaporation (REV) and compared to timolol solution (TMS; 0.25%) in terms of in vitro release and IOP lowering pharmacodynamic effect. The in vitro release phase of timolol (91% release in 2 h) was extended significantly by its incorporation into niosomes and further by the polymer coating (40-43% release upto 10 h). The developed formulations were evaluated for their pharmacodynamics in albino rabbits, by measuring intraocular pressure (IOP) using a non-contact pneumatonometer, and were compared to a marketed in situ gel forming solution of timolol (Timolet GFS, 0.5%; Sun Pharma). REVTMbio1 formulation showed a more sustained effect of upto 8h (vis a vis 6 h for carbopol-coated niosomes). TMS in comparison showed effect for only 2 h though the peak effect was slightly more (14%). Lowering of IOP in the contralateral eye (20-40% as compared to 100% in case of TMS), considerably reduces with REV and REVbio formulations indicating lesser systemic side effects. Moreover, the results of REVTMbio1formulation containing 0.25% of timolol maleate compared well with the 0.5% marketed gel formulation, indicating our formulation to be significantly better considering that similar effect is obtained at half the concentration. The later becomes especially important in context to the cardiovascular side effects associated with ocular timolol maleate therapy.

Adhesives↗

PubMed2004

24-Hour IOP control with once-daily bimatoprost, timolol gel-forming solution, or latanoprost: a 1-month, randomized, comparative clinical trial.

PURPOSE: To compare the efficacy and safety of once-daily (QD) bimatoprost, latanoprost, and timolol gel-forming solution in providing 24-hour intraocular pressure (IOP) control. DESIGN: This was a randomized, multicenter, investigator-masked, prospective, parallel-group, clinical trial. PARTICIPANTS: Patients with open-angle glaucoma or ocular hypertension. INTERVENTION: After washout of any previous ocular hypotensive medications, patients were randomly assigned to treatment with bimatoprost 0.03% ophthalmic solution QD (n=38) or latanoprost 0.005% ophthalmic solution QD (n=38) between 7 and 9 pm, or timolol maleate 0.5% gel-forming ophthalmic solution QD (n=39) between 7 and 9 am for 1 month. MAIN OUTCOME MEASURES: The primary outcome measure, circadian IOP, was measured at eight time points over the course of 24 hours beginning at 8 am on day 28 and with the last measurement at 8 am on day 29. IOP was also measured at 8 am and 10 am at baseline and at 8 am on day 14. Safety measures included adverse events, biomicroscopy, visual acuity, heart rate, and blood pressure. RESULTS: At 10 am (peak drug effect) on day 28, the mean IOP reduction from baseline was significantly greater with bimatoprost (9.3 mm Hg, 40.3%) than with timolol gel (7.1 mm Hg, 31.1%; P=.024, Wilcoxon rank sum test) or latanoprost (7.4 mm Hg, 33.3%). In the overall analysis of IOP measured over the course of 24 hours, mean IOP was significantly lower with bimatoprost or latanoprost than with timolol gel (P<.001; analysis of repeated measures). The analysis of repeated measures also showed a significant difference between bimatoprost and latanoprost (P=.003). In the area-under-the-curve analysis, bimatoprost and latanoprost were superior to timolol gel (P< or =.018) but comparable to each other (P> or =.223). All treatment regimens were well tolerated, with few discontinuations due to adverse events. There were no significant effects on systemic safety parameters. CONCLUSION: Once-daily bimatoprost or latanoprost provided significantly better 24-hour IOP control than timolol gel in patients with glaucoma or ocular hypertension. Some measurements suggested a trend for greater efficacy of bimatoprost over latanoprost. All three treatments were well tolerated.

Amides↗

PubMed2000

Long-term intraocular pressure-lowering efficacy and safety of timolol maleate gel-forming solution 0.5% compared with Timoptic XE 0.5% in a 12-month study.

PURPOSE: To evaluate the long-term intraocular pressure-lowering efficacy and safety of timolol maleate gel-forming solution 0.5% (Timolol GFS 0.5%, Alcon Research Ltd, Fort Worth, Texas) compared with Timoptic XE 0.5% (Merck, Inc, West Point, Pennsylvania) in patients with open-angle glaucoma or ocular hypertension. METHODS: Two hundred forty-one patients with open-angle glaucoma or ocular hypertension, who had intraocular pressure between 22 and 36 mm Hg in at least one eye, were randomly assigned in a 2:1 ratio to receive either Timolol GFS 0.5% once daily or Timoptic XE 0.5% once daily, in a 12-month randomized, multicenter, double-masked, prospective study. The primary efficacy variable was mean trough intraocular pressure measured at 8:00 AM, approximately 24 hours after dosing. RESULTS: The Timolol GFS 0.5% group produced significant trough intraocular pressure reductions from a baseline of 4.5 to 5.2 mm Hg (P =.0001), compared with reductions of 4.1 to 5. 3 mm Hg (P =.0001) in the Timoptic XE 0.5% group. The difference in mean intraocular pressure between the two treatments was 0.9 mm Hg or less, and the upper 95% confidence limit between groups was 0.92 mm Hg or less at all time points, demonstrating both clinical and statistical equivalence. A similar percentage of patients in the Timolol GFS 0.5% group (71%) and Timoptic XE group (72%) had clinically relevant reductions in intraocular pressure. There was no significant difference in the safety profiles of the two treatments. CONCLUSION: Both treatments were clinically effective in lowering intraocular pressure and maintaining the reductions over long-term use. Timolol GFS 0.5% is a safe and effective therapy for open-angle glaucoma or ocular hypertension and is both clinically and statistically equivalent to Timoptic XE 0.5% in reducing intraocular pressure.

Adrenergic beta-Antagonists↗

PubMed1999

Effects of carteolol and timolol on plasma lipid profiles in older women with ocular hypertension or primary open-angle glaucoma.

PURPOSE: To determine the effect on serum lipid levels of carteolol hydrochloride 1.0% or timolol maleate 0.5% given twice a day to women age 60 years and older with primary open-angle glaucoma or ocular hypertension. METHOD: We included 112 patients in this double-masked, randomized, multicenter trial. Fasting clinical laboratory studies were evaluated at baseline and at 12 weeks. Patients were instructed not to change their dietary, alcohol consumption, or exercise habits during the study. RESULTS: For the carteolol group, the high-density lipoprotein (HDL) and total cholesterol/high-density lipoprotein (TC/HDL) ratio at baseline of 50.1 +/- 1.5 mg/dl and 4.7 +/- 0.2 changed by the 12-week visit to 51.3 +/- 1.9 mg/dl (P = .25) and 4.6 +/- .02 (P = .47), respectively. For the timolol maleate group, the baseline HDL and TC/HDL ratio of 53.6 +/- 2.2 mg/dl and 4.4 +/- 0.2 changed to 50.2 +/- 1.9 mg/dl (P < .001) and 4.7 +/- 0.2 (P = .001), respectively, at the 12-week visit. Carteolol patients showed no significant change from baseline, whereas the HDL (P < .001) and TC/HDL ratio decreased (P = .001) significantly in the timolol maleate group. There also was a significant difference in the change from baseline at 12 weeks between carteolol and timolol maleate groups for the HDL and TC/HDL ratio (P = .01 and .012, respectively). No differences in TC, low-density lipoprotein (LDL), or triglycerides (TG) or in changes from baseline were observed between groups at 12 weeks (P > .05). At 12 weeks, no differences were observed between carteolol and timolol maleate groups in intraocular pressure or safety (P > .05), except that patients given carteolol demonstrated fewer solicited ocular symptoms (P = .007). CONCLUSIONS: Carteolol appears to be neutral in its effect on serum lipid levels, whereas timolol maleate adversely affects the HDL and TC/HDL ratio in women age 60 years and older with ocular hypertension or primary open-angle glaucoma.

Adrenergic beta-Antagonists↗

PubMed2002

The effect of latanoprost compared with timolol in African-American, Asian, Caucasian, and Mexican open-angle glaucoma or ocular hypertensive patients.

OBJECTIVE: To study the intraocular pressure (IOP) reduction of latanoprost or timolol in a heterogeneous global population. METHODS: A total of 1,389 glaucoma or ocular hypertensive patients treated with 0.005% latanoprost once daily (n = 737) or 0.5% timolol twice daily (n = 652) from eight clinical trials were included. After 3-6 months of treatment, the IOP was analyzed with use of analysis of covariance. RESULTS: Latanoprost or timolol gave statistically significant mean diurnal IOP reduction in the African-American, Asian, Caucasian, and Mexican patients, latanoprost with 7.9 mm Hg and timolol with 6.4 mm Hg. The Asian and Mexican patients showed a larger difference in mean diurnal IOP reduction with use of the two drugs (range 1.8-3.1 mm Hg) than the European and U.S. patients (range 0.6-1.7 mm Hg, p = 0.030). Latanoprost produced similar mean diurnal IOP reduction in patients with and without previous glaucoma treatment other than prostaglandins. CONCLUSION: Latanoprost or timolol statistically significantly reduced the mean diurnal IOP in a heterogenous global population in eight clinical trials. The degree of reduction appeared to be clinically useful. The greatest difference in the mean diurnal IOP-lowering effect of latanoprost or timolol was observed in Mexican and Asian clinical trials.

Adolescent↗

PubMed2000

Adjunctive therapy with brinzolamide 1% ophthalmic suspension (Azopt) in patients with open-angle glaucoma or ocular hypertension maintained on timolol therapy.

This prospective, multicenter, double-masked, placebo-controlled study evaluated the safety and efficacy of brinzolamide 1% ophthalmic suspension (Azopt) when used adjunctively with open-label timolol maleate 0.5% (Timoptic). One-hundred-thirty-two patients requiring an adjunctive therapy to timolol 0.5% for the treatment of open-angle glaucoma or ocular hypertension were randomized to receive brinzolamide or placebo three times daily (t.i.d.) in addition to timolol 0.5% twice daily (b.i.d.) for 3 months. Qualifying intraocular pressure (IOP) on timolol 0.5% b.i.d. was 24-36 mm Hg in at least one eye at 8:00 A.M. and 21-36 mm Hg at 10:00 A.M., with no greater than a 5-mm Hg difference between eyes, during two eligibility visits separated by at least 7 days. Treatments were compared using a repeated-measures analysis of variance. Adjunctive therapy with brinzolamide resulted in clinically and statistically significant reductions in IOP from the timolol baseline at all visits. IOP changes from a diurnal baseline ranged from -3.3 mm Hg to -4.1 mm Hg for brinzolamide (N = 53) compared with -0.9 mm Hg to -2.5 mm Hg for placebo (N = 55). Abnormal taste (7.7%) and transient blurred vision (6.2%) were the most frequently reported adverse events. No clinically significant differences in the incidence or severity of ocular signs, visual acuity, cup/disk ratio, or parameters studied on dilated fundus examination were observed between treatment groups. Brinzolamide 1% t.i.d., used adjunctively with timolol 0.5% b.i.d., is safe and well tolerated, and produces clinically and statistically significant additional IOP reductions.

Adrenergic beta-Antagonists↗

PubMed2000

Comparison of the intraocular pressure-lowering effect of latanoprost and timolol in patients with chronic angle closure glaucoma: a preliminary study.

OBJECTIVE: To compare the intraocular pressure (IOP)-reducing effect and side effects of 0.005% latanoprost once daily to 0.5% timolol twice daily in patients with primary chronic angle closure glaucoma (CACG). DESIGN: Randomized, double-masked two-center clinical trial. PARTICIPANTS: Thirty-two Asian patients with CACG, defined as glaucomatous optic neuropathy with a compatible visual field defect and at least 6 clock hours of synechial angle closure on gonioscopy were recruited. All patients had previous peripheral iridotomy (PI) with IOP >21 mmHg after PI and were thereafter controlled (IOP <22 mmHg) with one or two pressure-reducing drugs. INTERVENTION: After a washout period, the patients were randomized to a 2-week treatment period with either placebo in the morning and 0.005% latanoprost in the evening or 0.5% timolol twice daily. MAIN OUTCOME MEASURES: The short-term IOP reduction of latanoprost and timolol in patients with CACG. IOP was measured at baseline, and after 2, 7, and 14 days of treatment. In addition, the short-term ocular and systemic adverse events of the two drugs were evaluated. RESULTS: Thirty patients completed the study. Two patients in the timolol group were withdrawn because of inadequate IOP control. Compared with baseline, the IOP after 2 weeks of treatment was statistically significantly reduced by 8.8 +/- 1.1 mmHg (mean +/- SEM, P < 0.001) in the latanoprost group, and by 5.7 +/- 0.9 mmHg (P < 0.001) in the timolol group. The difference in IOP reduction between the two treatment groups was 3.1 +/- 1.5 mm Hg in favor of latanoprost (P = 0.04). The main ocular adverse events reported in both treatment groups were conjunctival hyperemia and discomfort. CONCLUSIONS: In this preliminary study, a significantly greater IOP reduction was achieved with 0.005% latanoprost once daily compared with 0.5% timolol twice daily in patients with CACG. The results suggest that latanoprost may be a therapeutic choice for the medical treatment of primary CACG.

Adrenergic beta-Antagonists↗

PubMed2000

Effects of systemic beta-blocker therapy on the efficacy and safety of topical brimonidine and timolol. Brimonidine Study Groups 1 and 2.

PURPOSE: To determine the impact of coadminstration of systemic beta-blockers on the ocular hypotensive efficacy and safety of topical timolol, a nonselective, beta-blocker, and that of brimonidine, an alpha2-selective adrenergic agonist, in patients with glaucoma or ocular hypertension. DESIGN: Post hoc evaluation of data collected from two prospective, multicenter, randomized, double-masked, parallel-group, actively-controlled, 12-month clinical trials. PARTICIPANTS: Of the 926 subjects with ocular hypertension or glaucoma that were enrolled in the two prospective trials, 66 (7.1%) were concurrently maintained on systemic beta-blocker therapy. Of these patients, 34 had been assigned to the brimonidine group and 32 to the timolol group. METHODS: Subjects instilled into each eye either 1 drop of brimonidine 0.2% or timolol 0.5% twice daily for 1 year. Study subjects within medication treatment groups were classified as to their use or nonuse of concurrent systemic beta-blockers, and mean intraocular pressure (IOP) reduction, adverse events, heart rate, and blood pressure were compared. MAIN OUTCOME MEASURES: Mean IOP reduction from baseline was the primary efficacy variable. Adverse events and mean changes in heart rate and blood pressure from baseline were the primary safety variables. RESULTS: Timolol-treated subjects concurrently taking systemic beta-blockers had smaller decreases in IOP, a greater mean change in systolic (at week 2, months 1, 2, 6, and 9; P < or = 0.001) and diastolic blood pressure (months 2 and 6; P < or = 0.02), and a significantly greater mean decrease in heart rate (month 6; P = 0.004) compared with timolol subjects not taking systemic beta-blockers. By contrast, there was a modest enhancement of IOP-lowering efficacy at trough and no effect on blood pressure or heart rate in brimonidine-treated subjects who were concurrently receiving systemic beta-blocker therapy compared with brimonidine subjects not receiving systemic beta-blockers. CONCLUSIONS: Concurrent systemic beta-blocker therapy had no deleterious effect on ocular hypotensive efficacy and no impact on systemic safety parameters with topical brimonidine, whereas efficacy was reduced and systemic safety parameters were impacted with topical timolol. Ocular hypotensive agents other than beta-blockers, such as the alpha2 agonist brimonidine, may be a more appropriate first-line therapy for ocular hypertension and glaucoma patients concurrently taking systemic beta-blockers.

Administration, Oral↗

PubMed1992

Effect of timolol versus pilocarpine on visual field progression in patients with primary open-angle glaucoma.

BACKGROUND: Relatively few studies have been conducted linking decreasing intraocular pressure (IOP) to preservation of visual field. This investigation was conducted to determine if this link could be made and to compare the long-term effect of two ocular hypotensive agents on preservation of visual field. METHODS: In an observer-masked study, 189 patients with primary open-angle glaucoma received either timolol or pilocarpine by random allocation. The dose of antiglaucoma agent was increased from 0.25% to 0.5% twice daily for timolol or from 2% to 4% four times daily for pilocarpine if the initial IOP response was inadequate. After an on-treatment baseline, visual fields were followed every 4 months for 2 years using the Octopus program 32. RESULTS: Compared with timolol, significantly more patients receiving pilocarpine discontinued use because of inadequate IOP control (P < or = 0.01). By comparing the mean visual field scores, it can be seen that the pilocarpine group had a significantly worse score at all timepoints from month 4 to month 24. The pilocarpine group also had a greater mean number of test loci with decreased sensitivity of 5 or more decibels (dB) at all timepoints. The mean within-patient regression slope for timolol was 0.01 dB/month and for pilocarpine was -0.06 dB/month (P < 0.01). The study has shown that over a 2-year period, patients treated with pilocarpine 2% or 4% four times daily experienced a significantly greater visual field deterioration than that seen in patients receiving either 0.25% or 0.5% timolol twice daily. CONCLUSION: Although these data do not support a link between lowering of IOP and visual field preservation, treatment with timolol was associated with significantly less visual field loss than treatment with pilocarpine.

Double-Blind Method↗

PubMed1993

Can the concentration of timolol or the frequency of its administration be reduced?

BACKGROUND: There is evidence that the ocular hypotensive effect of topical beta-blockers persists for at least 24 hours once beta-blockade has been achieved. In previous studies, the highest concentration of drug generally has been used for this purpose. METHOD: Home tonometry was performed with a self-tonometer by 14 patients to study the intraocular pressure (IOP) reduction of 0.5% timolol administered once daily in the morning or in the evening and of 0.25% timolol administered in the morning. The study was masked and included washout periods before and between the different regimens. At the end of each treatment period, the IOP was monitored five times daily for 3 days. RESULTS: No significant difference in mean reduction of IOP was found between the morning instillation of once daily 0.5% timolol compared with evening instillation of 0.5% timolol. In addition, there was no statistically significant difference in the mean IOP reduction between once daily administration of 0.25% versus 0.5% timolol. CONCLUSION: This study indicates that a lower concentration of timolol maleate used once daily may achieve maximum IOP reduction. The time of the single administration appears not to make any difference.

Adult↗

PubMed1996

Comparison of latanoprost and timolol in patients with ocular hypertension and glaucoma: a six-month masked, multicenter trial in the United States. The United States Latanoprost Study Group.

PURPOSE: Latanoprost, a new prostaglandin analogue, was compared with timolol for ocular hypotensive efficacy and side effects. METHODS: In a multicenter, randomized, double-masked, parallel group study, 268 patients with ocular hypertension or early primary open-angle glaucoma received either 0.005% latanoprost once daily or 0.5% timolol twice daily for 6 months. All except ten patients from each group successfully completed the study. RESULTS: Intraocular pressure (IOP) was significantly (P<0.001) reduced and maintained by both medications without evidence of a long-term drift over 6 months. Comparing 6-month with baseline diurnal IOP values, the IOP reduction (mean +/- standard deviation) achieved with latanoprost (-6.7 +/- 3.4 mmHg) was significantly (P<0.001) greater than that produced with timolol (4.9 +/- 2.9 mmHg). Four patients treated with timolol and none treated with latanoprost were withdrawn from the study because of inadequate IOP control. Pulse rate was significantly reduced with timolol, but not with latanoprost. Slightly more conjunctival hyperemia appeared in latanoprost-treated compared with timolol-treated eyes. Fewer subjective side effects occurred in latanoprost-treated eyes. Both eyes of a patient with a characteristic, concentric iris heterochromia (darker centrally) at baseline showed a definite, photographically documented increase in pigmentation during latanoprost treatment, making the irides uniformly darker. Three additional patients treated with latanoprost were suspects for this color change. Otherwise, no significant difference between treatment groups occurred visual acuity, slit-lamp examination, blood pressure, and laboratory values. CONCLUSION: Latanoprost has the potential for becoming a new first-line treatment for glaucoma.

Adrenergic beta-Antagonists↗

PubMed1985

Effect of timolol on the sympathetic nervous system in coronary occlusion in cats.

Clinical studies have shown that treatment with chronic timolol after a myocardial infarction decreases the incidence of reinfarction and mortality. It also limits the size of infarction when it is given IV during the acute phase of an infarction and followed by chronic oral dosing. It has been postulated that beta blockers work not only by a direct mechanism on the heart, but by altering neural discharge to the heart and depressing the sympathetic overactivity seen in 35% of patients immediately after an infarction. Our study examined the effect of timolol on sympathetic cardiac neural discharge, blood pressure, heart rate, and rhythm during acute coronary occlusion produced by ligation of the left anterior descending artery 10 to 14 mm below its origin in alpha-chloralose-anesthetized cats. Timolol or normal saline 5 mg/kg IV was given five minutes post coronary occlusion. The infusion of timolol significantly decreased the mean arterial blood pressure and heart rate. Sympathetic cardiac neural discharge in the group treated with timolol five minutes post coronary occlusion did not differ from that in the saline group. Thus there was a nonuniform (an increase, a decrease, or no change) sympathetic cardiac neural discharge associated with the production of occlusion-induced arrhythmia. These data suggest that the action of timolol on the sympathetic cardiac neural discharge is not its major mode of protection.

Animals↗

PubMed2001

Intraindividual comparison of the effects of a fixed dorzolamide-timolol combination and latanoprost on intraocular pressure after small incision cataract surgery.

To compare the effect of a fixed dorzolamide-timolol combination with that of latanoprost on intraocular pressure (IOP) after small incision cataract surgery. Department of Ophthalmology, University of Vienna, Vienna, Austria. This prospective randomized study comprised 60 eyes of 30 patients scheduled for small incision cataract surgery in both eyes. The patients were randomly assigned to receive 1 drop of a fixed dorzolamide-timolol combination or latanoprost immediately after cataract surgery in the first eye. The second eye received the other antiglaucomatous agent. Cataract surgery was performed under sodium hyaluronate 1% with a temporal 3.5 mm sutureless posterior limbal incision, phacoemulsification, and implantation of a foldable intraocular lens. The IOP was measured preoperatively as well as 6 and 20 to 24 hours and 1 week postoperatively. Six hours after surgery, the mean IOP decreased by -0.8 mm Hg +/- 3.2 (SD) (P =.184) in the dorzolamide-timolol group and increased by 3.6 mm Hg +/- 3.5 (P <.001) in the latanoprost group. Twenty to 24 hours after surgery, the mean IOP decreased by -2.8 +/- 2.4 mm Hg (P <.001) in the dorzolamide-timolol group and increased by 0.6 +/- 3.5 mm Hg (P =.353) in the latanoprost group. The differences between groups were significant at 6 hours (P <.001) and 20 to 24 hours (P <.001). The fixed dorzolamide-timolol combination was more effective than latanoprost in reducing IOP after small incision cataract surgery. Only the fixed dorzolamide-timolol combination prevented a postoperative IOP increase and occasional IOP spikes of 30 mm Hg or higher.

Antihypertensive Agents↗

PubMed2003

Effect of a fixed dorzolamide-timolol combination on intraocular pressure after small-incision cataract surgery with Viscoat.

PURPOSE: To evaluate the effect of a fixed dorzolamide-timolol combination (Cosopt) on intraocular pressure (IOP) after small-incision cataract surgery with sodium chondroitin sulfate 4%-sodium hyaluronate 3% (Viscoat). SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This prospective randomized study comprised 76 eyes of 38 patients scheduled for small-incision cataract surgery in both eyes. Patients were randomized to receive 1 drop of the fixed dorzolamide-timolol combination in 1 eye or no treatment (control) immediately after cataract surgery. The fellow eye received the other assigned treatment. Cataract surgery was performed with Viscoat in an identical fashion in both eyes. The IOP was measured preoperatively and 6 hours, 20 to 24 hours, and 1 week postoperatively. RESULTS: Six hours after surgery, the mean increase in IOP was significantly lower in the dorzolamide-timolol group than in the control group (4.3 mm Hg +/- 5.6 [SD] versus 8.4 +/- 6.1 mm Hg; P =.003). Two eyes in the dorzolamide-timolol group and 9 in the control group had IOP spikes of 30 mm Hg or higher (P =.022). Twenty to 24 hours after surgery, the mean IOP change was -2.6 +/- 3.3 mm Hg in the dorzolamide-timolol group and 1.5 +/- 3.2 mm Hg in the control group (P<.001). CONCLUSIONS: The fixed dorzolamide-timolol combination was effective in reducing IOP 6 hours and 20 to 24 hours after cataract surgery. However, it did not prevent Viscoat-induced IOP spikes of 30 mm Hg or higher.

Aged↗

PubMed2000

Water-activated, pH-controlled patch in transdermal administration of timolol. I. Preclinical tests.

Previously, transdermal patches with internal pH-controlled release were described. The aim of this study was to test the suitability of the patch design in transdermal delivery and, further, to select such transdermal patch formulations to a clinical study with timolol. In vitro release of timolol from the patches was determined as well as timolol permeation across the human cadaver skin. The effect of the skin on drug release were evaluated in vitro. In vitro data and pharmacokinetic parameters from the literature were used to construct a pharmacokinetic model for the prediction of in vivo performance of the devices. With water-activated, pH-controlled silicone reservoir devices, both the rate of drug release and the duration of constant release were controlled. The rate of timolol release was decreased when the devices were placed on human cadaver skin, and thus, the skin partly controls the rate and extent of timolol delivery to the systemic circulation in vivo. On the basis of in vitro data and kinetic simulations, devices of 10-cm(2) volume releasing timolol in vitro at the rates of 119 and 10 microgh(-1)cm(-2) were selected for human tests.

Administration, Cutaneous↗

PubMed1999

A comparative study on the effects of apraclonidine and timolol on the ophthalmic blood flow velocity waveforms.

PURPOSE: To evaluate the effects of topical timolol and apraclonidine on retrobulbar blood flow velocity waveforms in a group of healthy volunteers. METHODS: Apraclonidine 1% and timolol maleate 0.5% single dose administrations were crossed over double masked in 12 healthy volunteers. The intraocular pressure measurements were followed by Doppler examination of the ophthalmic artery and the central retinal artery. RESULTS: Intraocular pressure was reduced significantly on both treated and fellow eyes after timolol (p = 0.003, p = 0.04 respectively) and after apraclonidine (p = 0.002, p = 0.01 respectively). After apraclonidine administration end diastolic velocity, mean velocity decreased and pulsatility index increased in the ophthalmic artery of both treated and fellow eyes. Resistivity index increased and peak systolic velocity decreased only in the ophthalmic artery of treated eyes. All Doppler indices remained nonsignificant for central retinal artery of both eyes. After timolol administration there were no significant changes of the Doppler indices in the ophthalmic artery and central retinal artery of the treated and fellow eyes. CONCLUSION: Topical timolol and apraclonidine significantly reduced the intraocular pressure. Single dose administration of apraclonidine 1% increased the vascular impedance distal to the ophthalmic artery. On the other hand, timolol 0.5% had no effect on vascular impedance.

Adrenergic alpha-Agonists↗