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PubMed1993

Intraocular pressure reduction and systemic absorption of timolol after administration of one side-coated inserts in rabbits.

The object of this study was to test whether flat, circular ophthalmic inserts releasing drug only from one side, would show improved activity parameters and reduced systemic absorption. To this purpose, uncoated and one-side coated hydroxypropylcellulose inserts containing timolol were prepared and evaluated. An acrylic copolymer (Eudragit RS) was used as coating material. Timolol release from inserts was studied both in vitro and in vivo. Timolol release in vitro from the coated inserts was much slower than from the uncoated ones, due to the smaller releasing surface area. Compared with timolol eyedrops (0.5%, 50 microliters), administration of 250 micrograms of timolol in uncoated or coated inserts produced a significantly greater hypotensive effect at 6 and 8 hr post instillation in rabbits with artificially increased intraocular pressure. The coated inserts containing 62.5 micrograms of timolol antagonised isoproterenol-induced ocular hypotension significantly more than timolol eyedrops (0.5%, 12.5 microliters) and uncoated inserts containing 62.5 micrograms of timolol. Both uncoated and coated inserts provided a significant sustaining of timolol release in tear fluid and decreased systemic peak concentrations of timolol with respect to the eyedrop control. However, one-side coated inserts failed to show significant improvements with respect to the uncoated samples.

Absorption↗
PubMed2001

Effect of timolol on anterior optic nerve blood flow in patients with primary open-angle glaucoma as assessed by the Heidelberg retina flowmeter.

PURPOSE: To evaluate the effect of 0.5% timolol maleate on the capillary circulation of the anterior optic nerve head in patients with primary open-angle glaucoma and to compare the results with those obtained in a healthy control group. PATIENTS AND METHODS: Twelve patients with nonprogressive glaucoma and 12 age- and sex-matched healthy volunteers were included in this prospective study. Optic nerve head perfusion was examined by the Heidelberg Retina Flowmeter (HRF) in both groups. A 3-week washout period preceded the baseline measurement in the glaucoma group, and ONH blood flow was assessed again after 3 weeks of bilateral topical timolol treatment and 2 hours after timolol application. RESULTS: Intraocular pressure decreased significantly with timolol (P < 0.001). The HRF flow values for patients with glaucoma were comparable to those for a control group at baseline (P = 0.25), 3 weeks after timolol therapy (P = 0.09), and 2 hours after timolol instillation (P = 0.15). The glaucoma group showed no statistically significant change in the HRF parameter flow as compared with baseline, either after 3 weeks of timolol treatment or 2 hours after timolol instillation (P = 0.40). The heart rate and arterial systolic and diastolic blood pressure values showed no alteration after timolol therapy. CONCLUSIONS: Patients with nonprogressive glaucoma seem not to have an altered optic nerve blood flow as assessed by the HRF, and timolol treatment does not seem to alter the latter blood flow parameter in such patients.

Adrenergic beta-Antagonists↗
PubMed1991

Skin irritation induced by topically applied timolol.

1. Erythema induced by topically applied timolol, a non-selective beta-adrenoceptor blocker, was assessed in six male volunteers. Intensity of erythema developed on the inner surface of the left forearm where timolol free base was applied for 10 h was measured by a visual score, laser doppler flowmeter and reflectance spectrophotometry. Plasma timolol concentrations collected from the left and right arms were also measured. 2. The mean values for blood volume and blood flow per unit volume of tissue both of which were assessed by a laser doppler flowmeter, haemoglobin index measured by reflectance spectrophotometry, and magnitude of erythema graded by a visual score significantly increased after the application of an acrylic co-polymer adhesive patch containing 20% (w/v) timolol free base. 3. Plasma timolol concentrations collected from the left antecubital vein were 2.4 to 10.7 times greater than those from the right arm and had significant correlations (rs = 0.55 to 0.76) with the parameters indicating the extent of erythema developed where a patch containing timolol was applied. 4. The inter-individual variation of timolol was attributed to that of the diffusivity of timolol through skin rather than that of the skin reactivity to topically applied timolol because the plasma timolol concentrations drawn from the left arm in the subjects who did not develop erythema were very low.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1996

The intraocular pressure lowering effect of timolol in gel-forming solution.

The effect on the intraocular pressure (IOP) of 0.5% timolol solution given twice daily was compared to 0.5% timolol in gel-forming solution given once daily. Patients (n = 223) having an IOP of above 22 mmHg were recruited from 16 eye specialist centres in Scandinavia and Finland. The patients were randomized to two treatment groups, timolol solution treatment and timolol in gel-forming solution treatment. Eyes with and without pseudoexfoliation were included. The patients were stratified regarding the presence or not of pseudoexfoliation, to ensure appropriate distribution of this condition. No difference in intraocular pressure reducing effect was registered for the two groups. The pressure reducing effect of the two modes of treatment was not affected by the presence or not of pseudoexfoliation. The study also included registration of local and systemic signs and symptoms possibly related to the study medications. Blurring of vision occurred more often in patients given 0.5% timolol in gel-forming solution compared to timolol solution. The heart rate decreased statistically significantly in patients given timolol solution, but not in patients given timolol in gel-forming solution. This study suggests that treatment with 0.5% timolol in gel-forming solution once a day may be equally as good as 0.5% timolol solution given twice a day in patients with glaucoma both with and without pseudoexfoliation.

Adrenergic beta-Antagonists↗
PubMed2006

The cost-effectiveness of bimatoprost, latanoprost and timolol in treatment of primary open angle glaucoma in five European countries.

OBJECTIVE: The objective of this cost-effectiveness analysis is to evaluate cost-effectiveness ratios of the intraocular pressure (IOP)-lowering agents bimatoprost, latanoprost and timolol in five major European countries: France, Germany, Italy, Spain and the UK. METHODS: The cost-effectiveness analysis is based on achievement of IOP targets between 13 and 18 mm Hg. Thus, the cost-effectiveness ratios express the costs of having one patient successfully achieving IOP target. The perspective of the analysis is that of the health care sector payer, including costs of medicine and costs of ophthalmologist visits. The time frame is first year of glaucoma treatment. Four treatment strategies are analysed: Timolol as first line with add-on latanoprost or bimatoprost if IOP targets are not met, and latanoprost and bimatoprost as first line with add-on timolol. RESULTS: In the UK, Spain, Italy and Germany the timolol first with add-on of bimatoprost is the least expensive treatment. This strategy dominates both strategies involving latanoprost (as add-on to timolol or as first line) in these four countries. The incremental cost-effectiveness ratio of bimatoprost first-line therapy versus timolol with add-on bimatoprost varies from each country and target (from 305 pounds sterlings to 43,720 euros per patient). In France the timolol first line and latanoprost add-on is not dominated and is the cheapest alternative. The incremental cost-effectiveness ratio of timolol with add-on bimatoprost versus add-on latanoprost lies between 71 euros and 355 euros per patient depending on target (18 and 13 mm Hg, respectively). CONCLUSION: First-line treatment of latanoprost is dominated in all countries. In four out of five countries the timolol first-line therapy with add-on latanoprost is also dominated. Based on this pharmacoeconomic analysis, the most cost-effective strategy seems to be timolol first line with add-on bimatoprost if target is not met after 3 months.

Amides↗
PubMed1991

Ocular drug interactions involving topically applied timolol in the pigmented rabbit.

The objective of this study was to determine whether the ocular and systemic absorption of topically applied timolol in the pigmented rabbit was significantly affected by the coadministration with other eye medications, including pilocarpine, epinephrine, their prodrugs, phenylephrine, tetracaine, and proparacaine. Twenty-five microliters of 0.65% timolol maleate solutions, both in the presence and absence of a second drug, were instilled to the pigmented rabbit eye. Timolol concentrations in anterior segment tissues were monitored at 30 and 90 min, and the time course of timolol concentration in plasma was monitored over 120 min. All coadministered drugs except proparacaine reduced intraocular timolol concentrations by varying extents depending on the sampling time, while increasing the timolol concentrations in the conjunctiva and sclera. In addition, all coadministered drugs, except pilocarpine, tetracaine, and proparacaine, reduced the systemic absorption of timolol by an average of about 50%. A plausible explanation for the simultaneous reduction in ocular and systemic timolol absorption is changes in tear turnover rate, protein secretion, and binding of timolol to tear proteins, rather than changes in corneal and perhaps conjunctival and nasal permeability, elicited by the second drug. Vasoconstriction on the conjunctival and nasal mucosae is an additional factor possibly contributing to the reduction in systemic timolol absorption by epinephrine, its prodrug, phenylephrine, and perhaps the pilocarpine prodrug. The clinical implication of the above findings is that before instituting combination or multiple drug therapy the possibility of changes in ocular and systemic absorption of the first drug by the second drug must be considered.

Absorption↗
PubMed1984

Effects of the (+/-)-, (+)- and (-)-forms of propranolol, timolol and metoprolol on noradrenergic transmission in the rat isolated right ventricle.

The effects of the (+/-)-, (+)- and (-)-forms of propranolol, timolol and metoprolol on noradrenergic transmission have been studied in the rat isolated right ventricle. (+)- And (-)-propranolol (10(-5) M) inhibited the accumulation of radioactivity from [3H]-noradrenaline. The decline in the spontaneous outflow of radioactivity, following loading of the tissue with [3H]-noradrenaline, was reduced by (+)- and (-)-propranolol (10(-5) M), (+)-timolol (10(-5) M), (-)-timolol (10(-6) - 10(-5) M) and (+)-metoprolol (10(-5) M). (+)-Propranolol, (+)-timolol (10(-6) M) and (+)- and (-)-metoprolol (10(-5) M) increased the decline in outflow of radioactivity evoked by field stimulation in the absence, but not in the presence, of lignocaine (10(-4) M), probably by decreasing nerve excitability. The ability of (-)-propranolol (10(-5) M) to increase the decline in evoked outflow was also reduced in the presence of lignocaine. (+)-Propranolol, (+)-timolol and (-)-metoprolol reduced the contractile response to field stimulation by a similar percentage in the absence or presence of lignocaine. The ability of (-)-propranolol and (+)-metoprolol (10(-5) M) to reduce contractile responses was decreased and abolished, respectively, by the addition of lignocaine. Evoked-outflow was not altered but contractile responses were inhibited by (-)-timolol (10(-7) - 10(-5) M) and (-)-metoprolol (10(-5) M). Contractile responses to isoprenaline were not altered by (+)-propranolol, (+)-timolol (10(-7) M) and (+)-metoprolol (10(-7) - 10(-6) M). (+)- Or (-)-propranolol (10(-7) M) and (+)-timolol (10(-6) M) had no effect on the rate of beating to isoprenaline but reduced the force whereas (+/-)-metoprolol (10(-7) M) had no effect on the force but reduced the rate of beating. The rate of beating and force responses to isoprenaline were reduced by (+/-)-, (+)-, (-)-propranolol (10(-6) M), (+/-)- or (-)-timolol (10(-7) - 10(-6) M), (+/-)-metoprolol (10(-6) M) and (-)-metoprolol (10(-7) - 10(-6) M). The data suggest that, in the rat isolated right ventricle, the (+)-isomers are active constituents of (+/-)-propranolol and (+/-)-timolol but not of (+/-)-metoprolol.

Animals↗
PubMed2001

Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema by topical timolol and its preservative in early postoperative pseudophakia.

OBJECTIVE: To investigate the effects of timolol maleate with preservative and its preserved (PV) and nonpreserved vehicles (NPV) (benzalkonium chloride) on the blood-aqueous barrier and angiographic cystoid macular edema (CME) in early postoperative pseudophakia. PATIENTS AND METHODS: Patients with ocular hypertension, normal tension glaucoma, and primary open-angle glaucoma who underwent surgery for cataracts. The study included a double-masked trial for timolol, PV, and NPV and a single-masked trial on the effect of diclofenac sodium and fluorometholone acetate on all three. The patients were divided into 6 groups, each of which were simultaneously administered the following different combinations of compounds: timolol and diclofenac (group A), timolol and fluorometholone (group B), PV and diclofenac (group C), PV and fluorometholone (group D), NPV and diclofenac (group E), and NPV and fluorometholone (group F). The 6 groups were then compared using a laser flare cell meter to determine the degree of disruption of the blood-aqueous barrier and fluorescein angiography to investigate angiographic CME. The differences in mean daily fluctuations in intraocular pressure were compared on the preoperative baseline day and for 5 weeks postoperatively. Twice daily administration of 0.5% timolol maleate or the vehicles was started 2 days before surgery, and continued until 5 weeks after surgery. Diclofenac or fluorometholone drops were instilled in the eyes 4 times preoperatively, on the day of surgery, and 3 times daily for 5 weeks postoperatively. RESULTS: The flare amount was higher on the third and seventh days in group B than in group D, but was the same after the seventh day. The incidence of angiographic CME was the same between both groups. These 2 factors were significantly lower in group F. These 2 factors were also significantly lower in the 3 groups that received diclofenac instead of fluorometholone, with no difference among these groups. The intraocular pressure decline was significant in groups that received timolol compared with groups that received PV or NPV. CONCLUSIONS: Timolol and its preservative, benzalkonium chloride, cause disruption of the blood-aqueous barrier in early postoperative pseudophakia and increased incidence of angiographic CME. The concurrent administration of nonsteroidal anti-inflammatory drug such as diclofenac prevents these adverse effects without interfering with the drop in intraocular pressure caused by timolol. The addition of benzalkonium chloride to timolol contributes considerably to these adverse effects. CLINICAL RELEVANCE: The present results suggest the cause of similar complications produced by other antiglaucoma eyedrops containing similar preservatives.

Administration, Topical↗
PubMed2002

Soft contact lenses capable of sustained delivery of timolol.

The aim of this work was to evaluate the influence of the composition and the application of an imprinting technique on the loading capability of weakly crosslinked hydroxyethyl methacrylate (HEMA) hydrogels, with a view to their use as reloadable soft contact lenses for administration of timolol. Hydrogels were prepared by dissolution of ethylene glycol dimethacrylate (EGDMA, 10 mM) in HEMA with or without methacrylic acid (MAA) or methyl methacrylate (MMA; 100-400 mM) and with or without timolol maleate (10 mg/mL), initiation of polymerization by addition of 2,2'-azo-bis(isobutyronitrile) (AIBN, 10 mM), injection in molds, and curing in an oven at 50-70 degrees C. Unreacted reagents were removed by boiling. The dry hydrogels were clear and fully polymerized with smooth, poreless surfaces and presented optimal mechanical properties. The hydrogels were then characterized by determination of their swelling and timolol release kinetics in 0.9% NaCl, phosphate buffer (pH 7.4) and artificial lacrimal fluid, and of the timolol loading capacity of both nonimprinted hydrogels and de-timololized imprinted hydrogels at various pHs. Both water uptake and timolol release exhibited Fickian kinetics, except in the case of hydrogels made with 400 mM MAA. Timolol diffusion into 0.9% NaCl from HEMA or HEMA/MMA was slow; release from HEMA/MAA into phosphate buffer or lacrimal fluid was faster and increased with the MAA content of the polymer. Timolol loading was significant for HEMA/MAA hydrogels (imprinted or not) at pH 5.5-7.5, and specially for imprinted hydrogels containing 100 mM MAA, which absorb 12 mg timolol/g dry hydrogel. The results indicate that the incorporation of MAA as comonomer increases the timolol loading capacity to therapeutically useful levels while retaining appropriate release characteristics.

Adrenergic beta-Antagonists↗
PubMed1990

Effects of epinephrine pretreatment and solution pH on ocular and systemic absorption of ocularly applied timolol in rabbits.

The ratio between ocular and systemic drug concentrations describes the relative safety of ophthalmic dosage forms of the same drug in terms of its systemic side effects. In this study, we evaluated the effects of epinephrine pretreatment and solution pH on the aqueous humor:plasma and iris-ciliary body:plasma ratios of peak timolol concentrations after ocular application of timolol. Timolol eyedrops (5 mg/mL, 25 microL) were applied ocularly in pigmented rabbits. Raising pH of the eyedrops from 6.2 to 7.5 did not affect the ratio between ocular and systemic peak drug concentrations, since both ocular and systemic concentrations of timolol were increased. Administration of epinephrine (20 mg/mL, 50 microL) 5 min prior to timolol eyedrop administration reduced the peak timolol concentrations in plasma 65-80%. Epinephrine did not affect the ocular concentrations of timolol. The decreased peak concentrations in plasma were due to the conjunctival and nasal vasoconstricting effects of epinephrine and to the subsequent slower absorption of timolol. Our study demonstrates that compared with currently available eyedrops (pH 6.9), the ocular:systemic concentration ratio of ophthalmic timolol can be improved four- to sixfold in rabbits by combining epinephrine-induced conjunctival and nasal vasoconstriction and improved ocular absorption from pH 7.5 eyedrops.

Absorption↗
PubMed1984

The effect of d-timolol on intraocular pressure in patients with ocular hypertension.

The stereoisomer form of timolol used in the treatment of glaucoma is l-timolol. Although d-timolol is a less potent beta-adrenergic receptor blocker than l-timolol, several laboratory studies have found that d-timolol has ocular hypotensive effects. Thus, d-timolol may be a useful therapeutic agent for glaucoma that has fewer systemic side effects than l-timolol. We conducted a randomized, double-masked, single-drop study of the effects of d-timolol and placebo on intraocular pressure in 34 patients with ocular hypertension. d-Timolol significantly lowered intraocular pressure for the six-hour duration of the study. No patients receiving the drug reported subjective side effects. There was no change in visual acuity, pupil size, or results of external ocular or slit-lamp examinations during the study. No changes in pulse rate or blood pressure were attributable to the drug.

Administration, Topical↗
PubMed1980

Effect of timolol on autonomic neural discharge associated with ouabain-induced arrhythmia.

The purpose of this study was to determine the effect of the beta-blocking agent timolol on postganglionic cardiac and preganglionic splanchnic sympathetic and vagal neural discharge, ouabain-induced arrhythmia, heart rate and mean arterial blood pressure. Cats were anesthetized with alpha-chloralose, given atropine, and pretreated with timolol (5 mg/kg, i.v. infused at a rate of 0.5 mg/kg/min for 10 min). Bolus injections of ouabain (25 microgram/kg, i.v.) were given every 15 min until the animals died; the first injection was given 15 min after the end of the timolol infusion. When compared with cats (n = 13) receiving only ouabain, timolol (n = 11 cats) increased the time to ouabain-induced arrhythmia and death from 23 +/- 3 to 48 +/- 7 and 46 +/- 3 to 76 +/- 9 min, respectively (p less than 0.05). Both heat rate and mean arterial blood pressure had decreased from 137 +/- 4 to 104 +/- 6 beats/min and 133 +/- 6 to 103 +/- 7 mm Hg, respectively (P less than 0.05); ouabain did not reverse the decreases. Neural activity monitored from the vagus and from the postganglionic cardiac and preganglionic splanchnic sympathetic nerves was not significantly altered by the infusion of timolol. The administration of ouabain after timolol did not alter splanchnic nor vagal discharge. Most important was the observation that postganglionic cardiac sympathetic neural discharge exhibited both increases and decreases, i.e., a nonuniform neural discharge, at the time of ouabain-induced arrhythmia and that the ouabain-induced nonuniformity did not occur in the cats pretreated with timolol. Thus, the protective effect of timolol may be due, in part, to prevention of the nonuniform postganglionic cardiac sympathetic neural discharge and to the prevention of ouabain-induced increases in vagal discharge. The establishment of beta-blockade and a direct negative inotropic action may also have contributed to the antiarrhythmic action of timolol.

Animals↗
PubMed1982

Infarct size restriction in cats by the beta-adrenergic blocker timolol.

The beta-adrenergic antagonist, timolol, was previously shown to exert a protective effect in cats subjected to 5 h of myocardial ischemia. The present study was designed to determine the effect of timolol on infarct size in cats 24 h after coronary occlusion. Timolol (25 microgram/kg) or vehicle (0.9% NaCl) was administered 0.5, 5, 10, 15 and 20 h after acute ligation of the left anterior descending coronary artery. There was no significant difference in arterial blood pressure or heart rate in MI cats receiving timolol or vehicle. Timolol markedly decreased S-T segment elevation at 2-12 h (P less than 0.05). Left ventricular weights in MI + vehicle cats (8.5 +/- 0.7 g, n = 6) were similar to timolol-treated MI cats (8.9 +/- 0.4 g, n = 7). However, the percent of the left ventricular myocardium infarcted, determined by nitroblue tetrazolium staining, was significantly less (P less than 0.001) in timolol MI cats compared to saline-treated cats, 9.8 +/- 1.2% (n = 7) vs. 18.9 +/- 1.8% (n = 6), respectively. Hemodynamic or cytoprotective actions of timolol do not appear to explain these results. Rather, the mechanism of infarct size reduction by timolol is probably explained by antagonism of beta-receptor-mediated metabolic effects.

Animals↗
PubMed2004

Improvement of the ocular bioavailability of timolol by sorbic acid.

The ocular bioavailability of timolol increased in sorbic acid solution due to ion pair formation. Its octanol/water partition coefficient also increased, suggesting the formation of a more lipophilic complex. The concentration of timolol in rabbit aqueous humor was determined after instillation of timolol ophthalmic solution containing sorbic acid. When the molar ratio of sorbic acid to timolol was two or higher, the concentration of timolol in the aqueous humor was higher than with timolol alone. In the presence of sorbic acid the maximal aqueous humor concentration and the area under the curve were more than two-fold higher than those of Timoptol, a timolol maleate ophthalmic solution, and similar in value to TIMOPTIC-XE, a gel-forming ophthalmic solution. To investigate the transcorneal absorption mechanism, in vitro permeation profiles across the intact and de-epithelialyzed cornea were analyzed on the basis of the bilayer diffusion model. The partition coefficient in the epithelium was about twice as high in the presence of sorbic acid than with timolol alone, although the diffusion coefficient in the epithelium did not change. We conclude that the improved ocular bioavailability in the presence of sorbic acid is due to increased partitioning of timolol in the corneal epithelium.

Administration, Topical↗
PubMed1983

Antianginal efficacy and improved exercise performance with timolol. Twice-daily beta blockade in ischemic heart disease.

Antianginal efficacy and improved exercise performance with timolol, a new beta-adrenergic blocking agent, was assessed in 23 patients with chronic stable angina pectoris in an 11-week double-blind, placebo-controlled study. Twenty-two of the 23 subjects completed the open-label phase of this investigation (weeks 0 to 6) while receiving 10 to 30 mg of timolol twice daily to optimize exercise capacity. Weekly anginal episodes and nitroglycerin consumption declined from 8.9 +/- 9.1 episodes/week and 8.1 +/- 10.6 tablets/week, respectively, with placebo to 2.7 +/- 5.2 episodes/week and 2.6 +/- 6.0 tablets/week with optimal timolol dose (p less than 0.05). Resting heart rate (HR) and systolic blood pressure (SBP) also decreased from 75.2 +/- 14.0 beats/min and 139.1 +/- 15.7 mm Hg with placebo to 55.1 +/- 8.9 beats/min and 130.5 +/- 15.9 mm Hg with timolol (p less than 0.05). Peak exercise HR, peak exercise SBP, and peak exercise double product (HR X SBP) were significantly (p less than 0.05) reduced when evaluated 12 to 13 hours after administration of timolol compared with placebo (101.5 +/- 21.1 beats/min verus 193.3 +/- 96.2 beats/min, 161.5 +/- 26.7 mm Hg versus 175.6 + 20.8 mm Hg, and 16.6 +/- 5.1 X 10(-3) versus 21.7 +/- 5.4 X 10(-3), respectively). Exercise duration was prolonged from 263.3 +/- 90.2 seconds to 330.3 +/- 73.9 seconds (p less than 0.05), while time to onset of 1 mm S-T segment depression was delayed in 15 patients from 231.8 +/- 86.4 seconds to 298.7 +/- 68.4 seconds (p less than 0.05). During the double-blind phase (weeks 7 to 10), 8 subjects received timolol and 11 patients received placebo. Nitroglycerin consumption at weeks 8 and 10 and anginal frequency at week 8 were unchanged compared with initial placebo treatment. Resting HR, peak exercise HR, and peak exercise double product were significantly attenuated at weeks 8 and 10 in timolol patients compared with their initial placebo exposure. However, these variables were unchanged in placebo subjects compared with their initial placebo therapy. Exercise duration was again prolonged at week 8 in timolol subjects compared with initial placebo results (315.1 +/- 61.2 seconds versus 261.3 +/- 68.8 seconds, p less than 0.05), but not at week 10. Placebo patients demonstrated no difference at week 8 or 10 in exercise performance compared with initial placebo treatment. Timolol twice daily, therefore, is potentially useful in some patients with angina pectoris. Other patients may, however, require a shorter dose interval for optimal angina control and maximal improvement in exercise capacity.

Administration, Oral↗
PubMed1997

Efficacy of carteolol hydrochloride 1% vs timolol maleate 0.5% in patients with increased intraocular pressure. Nocturnal Investigation of Glaucoma Hemodynamics Trial Study Group.

PURPOSE: To evaluate the ocular hypotensive effect and safety of carteolol hydrochloride 1% vs timolol maleate 0.5%. METHODS: One hundred seventy-six patients with ocular hypertension or primary open-angle glaucoma were randomly assigned to receive either carteolol 1% twice a day or timolol maleate 0.5% solution twice a day in a randomized, double-masked, multicenter, parallel-group, active-control comparison trial during a 3-month period. RESULTS: After 12 weeks, carteolol 1% reduced the mean +/- SE intraocular pressure from 25.0 +/- 0.3 to 19.5 +/- 0.3 mm Hg; timolol maleate 0.5% reduced the mean intraocular pressure from 25.2 +/- 0.3 to 19.6 +/- 0.3 mm Hg. The mean difference in trough intraocular pressure between carteolol and timolol maleate of -0.14 mm Hg was not significantly (P = .745) different (95% confidence limits, -0.97 to 0.70 mm Hg). Trough pulse and blood pressure also showed no consistent statistically significant differences between groups. The 2-hour postdose pulse, however, demonstrated a greater decrease in the timolol maleate than in the carteolol group (P < .001). Systemic and ocular signs and symptoms were similar between the groups except that the number of treatment-emergent reports of bradycardia was greater in the timolol maleate group (P = .039), and the carteolol group reported fewer ocular symptoms than the timolol maleate group did (P < .01). CONCLUSIONS: Both carteolol 1% and timolol maleate 0.5% are highly effective in lowering intraocular pressure when measured at the end of the dosing interval. Carteolol 1% demonstrates an ocular hypotensive effect and safety profile similar to those of timolol maleate 0.5% solution.

Adolescent↗
PubMed1998

Comparison of the effect of latanoprost 0.005% and timolol 0.5% on the calculated ocular perfusion pressure in patients with normal-tension glaucoma.

PURPOSE: To compare the calculated mean ocular perfusion pressure at the end of 3 weeks' treatment with latanoprost 0.005% once daily or timolol 0.5% twice daily in normal-tension glaucoma patients. METHODS: In a three-center, double-masked, randomized, crossover study, 36 patients were allocated to two treatment groups; one received 3 weeks each of placebo, latanoprost, placebo, and timolol, whereas the other group had placebo, timolol, placebo, and latanoprost. Intraocular pressure and resting systemic blood pressure were measured at 9 AM, 12 noon, and 4 PM. Ocular perfusion pressure was calculated for each time period as well as the mean of three values (daytime average). Systemic blood pressure and heart rate were also recorded at 30-minute intervals during the last 24 hours of each treatment period. RESULTS: The average daytime mean ocular perfusion pressure (mean +/- SEM) following latanoprost treatment was 53.2 +/- 1.4 mm Hg, an increase of 8% from the latanoprost run-in period, compared with 50.9 +/- 1.1 mm Hg following timolol treatment, an increase of 2% from the timolol run-in period (P < .05, ANOVA). Timolol reduced the blood pressure. The difference in mean daytime and nighttime systolic blood pressure measurements as well as nighttime diastolic blood pressure was about 5 mm Hg between the latanoprost and timolol treatments. The daytime and nighttime heart rates were also slower during the timolol treatment. CONCLUSION: Because ocular perfusion pressure may be important in some glaucomatous patients, latanoprost appears to affect ocular perfusion pressure more favorably than timolol does in patients with normal-tension glaucoma.

Adrenergic beta-Antagonists↗
PubMed2001

Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.

The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p </=.05). BID dosing of bimatoprost also provided significantly greater mean IOP reductions than timolol at most timepoints, but was not as effective as QD dosing. The IOP lowering provided by bimatoprost QD was sustained for 6 months. At month 6, the mean IOP reduction from baseline at 10 AM was 8.1 mm Hg (33%) with bimatoprost QD, 6.3 mm Hg (26%) with bimatoprost BID, and 5.6 mm Hg (23%) with timolol. Low target pressures were achieved by a significantly higher percentage of patients in the bimatoprost QD group than in the timolol group. At 10 AM (peak timolol effect) at month 6, IOP </= 17 mm Hg was achieved by 63.9% of bimatoprost QD patients, compared with 37.3% of timolol patients (p <.001). Bimatoprost was safe and well-tolerated, with few discontinuations due to adverse events. The most frequent side effect was trace-to-mild conjunctival hyperemia. Changes in iris pigmentation were reported in 1.1% of bimatoprost patients. There were no other significant findings in slit lamp examinations, ophthalmoscopy, visual acuity, or visual fields, and systemic safety parameters were also unaffected. Together these results indicate that bimatoprost QD is statistically and clinically superior to timolol in lowering IOP, and is safe and well-tolerated in patients with glaucoma or ocular hypertension.

Adrenergic beta-Antagonists↗