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PubMed2005

Efficacy and systemic side-effects of topical 0.5% timolol aqueous solution and 0.1% timolol hydrogel.

PURPOSE: The objective of this randomized, double-blind, controlled crossover trial was to compare 0.1% timolol hydrogel formulation eyedrops with 0.5% timolol aqueous solution in terms of systemic effects, hypotensive efficacy and pharmacodynamics. METHODS: Twenty-four healthy subjects underwent careful ocular, cardiovascular and pulmonary function evaluation before and after 2 weeks of topical treatment with 0.1% timolol hydrogel or 0.5% aqueous timolol maleate. Intraocular pressure (IOP), heart rate, blood pressure, forced expiratory volume and plasma levels of timolol were measured. RESULTS: There was a statistically significant difference in the systemic absorption of timolol between these two ophthalmic timolol solutions. The peak concentration and mean area under the plasma drug concentration-time curve (AUC) were about 10-fold higher after 0.5% timolol aqueous solution. The mean peak heart rate during exercise was reduced by 19 bpm (SD 6.4 bpm) after 0.5% timolol aqueous solution and by only 4.6 bpm (SD 3.8 bpm) after 0.1% timolol hydrogel (p < 0.0001). There was no difference between the two formulations in efficacy in reducing IOP. No differences between treatments were found in respect of pulmonary function. CONCLUSIONS: The lower timolol concentration in the hydrogel vehicle and its better bioavailability resulted in reduced systemic absorption and side-effects without loss of efficacy.

Absorption↗
PubMed1999

[The influence of 0.85% RS-timolol and 0.5% S-timolol on intraocular pressure and systemic arterial blood pressure, heart rate, ECG, expiratory capacity in patients with ocular hypertension and primary open-angle glaucoma].

PURPOSE: Analysis of local and systemic effects of RS-timolol enantiomer and S-timolol in patients with ocular hypertension and glaucoma: evaluation of Risk/Benefit Ratio. MATERIAL AND METHODS: 19 patients (38 eyes) receiving 0.85% RS-timolol and 10 patients (20 eyes) receiving 0.5% S-timolol were evaluated using a double-blank test. Intraocular pressure, heart rate, systemic arterial blood pressure, ECG and spirometry were recorded before and 2 hours after drugs administration and after 7 days of treatment. RESULTS: There were no statistically significant differences between intraocular pressure-lowering effects of RS-timolol and S-timolol. In patients receiving both medicines bradycardia was detected 2 hours after drugs administration. Patients receiving RS-timolol showed increased expiratory capacity in comparison to those receiving S-timolol. There was no detectable influence of both medicines on ECG and systemic arterial blood pressure. CONCLUSIONS: 0.85% RS-timolol and 0.5% S-timolol produced comparable intraocular pressure-lowering effects. 0.85% RS-timolol exerted less severe influence on respiratory system.

Adrenergic beta-Antagonists↗
PubMed2006

The effect of timolol-dorzolamide and timolol-pilocarpine combinations on ocular blood flow in patients with glaucoma.

PURPOSE: To investigate the effect of timolol-dorzolamide and timolol-pilocarpine fixed combinations on retrobulbar vessel blood flow. DESIGN: Prospective, randomized, masked, crossover clinical trial. METHODS: Sixteen patients with primary open angle glaucoma, treated with timolol 0.5%, received timolol 0.5%-dorzolamide 2% and timolol 0.5%-pilocarpine 2% for four weeks each. Heart rate, blood pressure, intraocular pressure (IOP), and peak systolic (PSV) and end diastolic velocities (EDV) in ophthalmic, central retinal, and short posterior ciliary arteries were measured before and after each treatment, and resistivity index was calculated. RESULTS: The IOP was reduced (P < .01) by timolol-dorzolamide and, more effectively, timolol-pilocarpine combinations. In central retinal artery, the end diastolic velocity was increased by the timolol-dorzolamide combination (P < .01), resulting in higher end diastolic velocity and lower resistivity index values (both P < .01) compared with the timolol-pilocarpine combination. CONCLUSIONS: The timolol-dorzolamide combination increases the end diastolic velocity in central retinal artery, despite a lower intraocular pressure decrease, suggesting an effect on retinal circulation.

Aged↗
PubMed1996

Timolol hemihydrate vs timolol maleate to treat ocular hypertension and open-angle glaucoma.

PURPOSE: We compared the therapeutic efficacy and safety of timolol hemihydrate to timolol maleate in patients with ocular hypertension and chronic open-angle glaucoma. METHODS: We conducted this three-month study as a multicentered, masked, parallel group comparison. Both the 0.25% and 0.5% concentrations were evaluated against similar concentrations of timolol maleate. Dosing was twice daily. An open-label, nine-month study followed the masked portion of the protocol, in which all patients received either 0.25% or 0.5% timolol hemihydrate. A total of 371 patients were included in both the 0.25% and 0.5% studies. RESULTS: We found statistically similar intraocular pressures with both the 0.25% (18.3 and 18.6 mm Hg for the hemihydrate and maleate groups, respectively) and 0.5% (19.9 and 19.5 mm Hg for the hemihydrate and maleate groups, respectively) concentrations of timolol hemihydrate and timolol maleate after three months of masked treatment. Likewise, peak intraocular effect at two hours after taking the medication was statistically similar between medicines at both concentrations. Likewise, both ocular and systemic safety were similar between the maleate and hemihydrate preparations at both concentrations. In the nine-month open-label protocol, therapeutic efficacy (19.9 and 19.1 mm Hg for the 0.25% and 0.5% concentrations, respectively) and safety of timolol hemihydrate were similar to effect and safety of the three-month protocol. CONCLUSIONS: This study suggests that timolol hemihydrate had an ocular hypotensive efficacy and safety profile statistically equivalent to that of timolol maleate for up to three months of therapy. Timolol hemihydrate showed efficacy and safety similar to that observed within the first three months, for up to one year of therapy.

Adolescent↗
PubMed1999

Efficacy and safety of timolol solution once daily vs timolol gel added to latanoprost.

PURPOSE: To compare the efficacy and safety of timolol hemihydrate 0.5% (Betimol, Ciba Vision Ophthalmics, Duluth, Georgia) vs timolol maleate gel-forming solution 0.5% (Timoptic-XE, Merck, Blue Bell, Pennsylvania), both given every morning added to latanoprost 0.005% given every evening. METHODS: A multicenter, randomized, crossover comparison was performed in patients with primary open-angle glaucoma or ocular hypertension. After at least a 4-week run-in period with latanoprost 0.005% (Xalatan, Pharmacia & Upjohn, Kalamazoo, Michigan), both eyes from 30 patients (60 eyes) were randomly assigned to one of the two adjunctive therapies, timolol hemihydrate or timolol maleate gel for 6 weeks. At the end of the first period, the study medicine was discontinued for a 2-week washout period. Patients then received the opposite medication for the second 6-week period. This study had an 80% power to exclude a 1-mm Hg difference between groups. RESULTS: The baseline intraocular pressure after 1 month of latanoprost treatment only for all 30 subjects was 20.8 +/- 2.6 mm Hg. After 6 weeks of timolol hemihydrate, the 24-hour trough intraocular pressure was 17.5 +/- 3.4 mm Hg, and for timolol maleate gel, 17.9 +/- 3.5 mm Hg (P = .74). The peak level 2 hours after dosing for timolol hemihydate was 16.4 +/- 2.6 mm Hg, and for timolol maleate gel, 16.8 +/- 3.8 mm Hg (P = .84). No patient was discontinued from the study because of lack of efficacy. No differences were observed between treatments in visual acuity, anterior segment findings, or adverse events. CONCLUSIONS: Once-daily beta-blocker therapy is an effective ocular hypotensive adjunctive treatment 24 hours after dosing when added to latanoprost, for which timolol hemihydrate 0.5% solution and timolol maleate gel 0.5% appear equally effective and safe.

Adolescent↗
PubMedDate not supplied

Comparison of the effects of topical administration of a fixed combination of dorzolamide-timolol to monotherapy with timolol or dorzolamide on IOP, pupil size, and heart rate in glaucomatous dogs.

OBJECTIVE: To determine whether the combination multiple-dose dorzolamide-timolol administered topically has any greater effects on the reduction of intraocular pressure, pupil size, and heart rate in dogs with glaucoma than do either timolol or dorzolamide alone. PROCEDURE: Applanation tonometry, pupil size, and heart rate measurements were made at 7 a.m., 1 p.m., and 7 p.m. daily of 12 laboratory Beagles with inherited primary open-angle glaucoma during each active phase of this study. Timolol 0.5% was administered first twice daily for 4 consecutive days. Dorzolamide 2.0% was administered next three times daily for 4 consecutive days. The fixed combination of the two (timolol 0.5% and dorzolamide 2.0%) was administered twice daily for 4 consecutive days during the final week of the study. Between administration of each drug, a withdrawal period of at least 10 days was instituted. Statistical comparisons between the effects of the three drugs were performed. RESULTS: Intraocular pressure (IOP) was decreased with the administration of all three drugs: timolol alone, dorzolamide alone, and the combination of the two decreased IOP after 1 day of treatment 2.83 +/- 0.70 mmHg, 6.47 +/- 0.32 mmHg, and 6.56 +/- 0.37 mmHg, respectively. After 4 days of treatment, the IOP decreased even further: timolol alone, dorzolamide alone, and the combination of the two decreased IOP 3.75 +/- 0.88 mmHg, 7.50 +/- 0.29 mmHg, and 8.42 +/- 0.58 mmHg, respectively. Heart rate was significantly decreased with timolol (-11.9 +/- 2.0 bpm) and the combination preparation (-8.6 + 2.4 bpm), but not with dorzolamide (-3.7 +/- 1.8 bpm) alone. Pupil size was significantly decreased with timolol (-1.42 + 0.40 mm) and the combination preparation (-1.3 + 0.33 mm), but not with dorzolamide (0.97 +/- 0.36 mm) alone. CONCLUSIONS: The combination dorzolamide-timolol appears to be more effective at reducing intraocular pressure in glaucomatous dogs than is either timolol or dorzolamide alone.

Administration, Topical↗
PubMed1998

Efficacy and safety of timolol solution once daily versus timolol gel in treating elevated intraocular pressure.

PURPOSE: To evaluate the efficacy and safety of timolol hemihydrate once daily versus timolol maleate gel forming solution once daily in patients with primary open-angle glaucoma or ocular hypertension. METHODS: We prospectively randomized patients with primary open-angle glaucoma or ocular hypertension to receive either timolol hemihydrate 0.5% solution or timolol maleate gel forming solution 0.5% every morning. The primary efficacy variable was the 8:00 AM trough intraocular pressure (IOP) 24 hours after administration. RESULTS: Three months after initiation of therapy, baseline IOP had decreased from 23.6 +/- 1.9 mmHg to 18.3 +/- 2.8 mmHg in the group taking timolol hemihydrate (n = 22) and from 23.7 +/- 2.2 mmHg to 18.4 +/- 3.1 mmHg in the group receiving timolol maleate gel (n = 21) at the 24-hour trough level. This was not a significant difference between groups at 3 months. Also, no difference was observed between groups in the 2-hour post instillation IOP. Visual acuity was decreased in the group receiving timolol maleate gel compared with those receiving timolol hemihydrate one minute after instillation of study medicine at month 3. Otherwise, ocular and systemic safety were similar between groups. No differences between groups in cardiac pulse or systolic and diastolic blood pressure were observed. CONCLUSION: Timolol hemihydrate 0.5% solution given once a day appears to be as efficacious and safe in decreasing IOP as timolol maleate gel 0.5% given once a day.

Blood Pressure↗
PubMed2006

24-Hour control with a latanoprost-timolol fixed combination vs timolol alone.

OBJECTIVE: To evaluate 24-hour intraocular pressure (IOP) control with an evening-dosed latanoprost-timolol maleate fixed combination vs timolol alone in patients with primary open-angle glaucoma. METHODS: After a medicine-free period, qualified patients were randomized to either placebo dosed in the morning with a latanoprost-timolol fixed combination dosed in the evening or timolol alone dosed twice daily for 8 weeks. Patients were then switched to the opposite treatment for 8 weeks. At baseline and at the end of each treatment period, patients underwent IOP measurements. RESULTS: Both treatments reduced the IOP from untreated baseline at each time point and for the 24-hour curve (P<.001). When treatments were compared, the latanoprost-timolol fixed combination decreased the IOP more than timolol alone at each time point and for the 24-hour curve (2.9 mm Hg), and provided a lower absolute IOP at each time point (P<.001) and for the range (fluctuation) in IOP (P = .003) and for the 24-hour curve. Several adverse effects were observed more often with the latanoprost-timolol fixed combination, including ocular stinging (P = .05), conjunctival hyperemia (P = .02), and ocular itching (P = .04). CONCLUSION: The evening-dosed latanoprost-timolol fixed combination may provide better IOP control than timolol alone over 24 hours and may demonstrate a narrower range of IOP fluctuation in patients with primary open-angle glaucoma.

Antihypertensive Agents↗
PubMed2001

Comparison of the corneal effects of latanoprost, fixed combination latanoprost-timolol, and timolol: A double-masked, randomized, one-year study.

OBJECTIVE: To compare the long-term effects on corneal endothelial cell density and corneal thickness of latanoprost and the fixed combination latanoprost-timolol to timolol. DESIGN: Double-masked, randomized, prospective, multicenter clinical trial. PARTICIPANTS: Three hundred sixty-nine subjects with bilateral ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density of at least 1500 cells/mm(2), central corneal thickness of less than 0.68 mm, no corneal pathologic condition on slit-lamp examination, and intraocular pressure of less than 22 mmHg after a 3-week run-in on timolol, 0.5%, once daily were included. INTERVENTION: Subjects were randomly assigned to treatment with latanoprost 0.005% (n = 127), fixed-combination latanoprost 0.005%-timolol 0.5% (FC, n = 116), or timolol 0.5% (n = 126) one drop, once daily in the morning for 1 year. All subjects were treated in both eyes. Specular microscopy and ultrasonic pachymetry were performed before treatment, and after 6 and 12 months of treatment. MAIN OUTCOME MEASURES: Mean percent change in central endothelial cell density and central corneal thickness after 1 year of treatment. RESULTS: For both corneal endothelial cell density and corneal thickness, the mean percent changes from baseline were similar in all three treatment groups. Mean percent endothelial cell change at 1 year from baseline for latanoprost, FC, and timolol was 0.3 +/- 2.2%, 0.1 +/- 1.8%, 0.0 +/- 2.5% (mean +/- standard deviation; 95% confidence interval: latanoprost vs timolol -0.2-1.0; FC vs timolol -0.4-0.7) and mean percent change in corneal thickness was -1.1 +/- 2.5%, -1.0 +/- 2.0%, 0.2 +/- 3.1%, respectively. CONCLUSIONS: Latanoprost and FC are equivalent to timolol regarding long-term corneal effects after 1 year of treatment.

Adult↗
PubMed1996

Timolol hemihydrate: a new formulation of timolol for the treatment of glaucoma.

Timolol maleate, a non-selective beta-adrenergic blocker, has been used to treat glaucoma and ocular hypertension for almost two decades. Recently a new preparation, timolol hemihydrate, has been described which eliminates the maleate buffer and simplifies the purification step for the R-enantiomer. The ocular pharmacology of the two medicines is expected to be similar. Ocular bioavailability as well as toxicity for timolol hemihydrate is similar to that which has been shown previously for timolol maleate. In a multicenter trial in the United States, timolol hemihydrate was shown to reduce the intraocular pressure to a similar extent as timolol maleate. At the week 12 visit intraocular pressure was 19.5 and 19.5 mm Hg for the hemihydrate and maleate groups respectively for the 0.25% concentration and 18.3 and 18.6 mm Hg respectively for the 0.5% concentration. Following a nine month open-label portion where patients were treated with timolol hemihydrate only intraocular pressure was 19.9 and 19.1 mm Hg for the 0.25% and 0.5% concentrations respectively. Ocular and systemic adverse events, as well as vital signs, were similar between timolol hemihydrate and maleate. In conclusion, timolol hemihydrate appears to be a safe and effective medicine in the treatment of ocular hypertension and chronic open-angle glaucoma.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Timolol 0.1% gel (Nyogel 0.1% once daily versus conventional timolol 0.5% solution twice daily: a comparison of efficacy and safety.

In a prospective, randomised, double-masked, parallel-group, multi-centre study, 210 patients with primary open angle glaucoma or ocular hypertension were enrolled of whom 167 (timolol 0.1% gel 82, timolol 0.5% 85) completed the study as per protocol. The change in intraocular pressure between baseline and week 12 in the worse eye ('at trough') was 6.3 (SD 3.3) mm Hg on timolol 0.1% gel and 7.0 (2.9) mm Hg on timolol 0.5%; this difference was not statistically significant (p = 0.19). The difference between the two study groups in the change of intraocular pressure from baseline was 0.62 mm Hg; the 90% CI of -0.09 to +1.33 mm Hg was within the pre-specified limits of -1.5 to +1.5 mm Hg demonstrating equivalence between timolol 0.1% gel and timolol 0.5%. The plasma levels of timolol (ng/ml) at 12 weeks in the timolol 0.1% gel group were significantly less than that with timolol 0.5% both before instillation (mean 0.057, SD 0.131 and mean 0.470, SD 0.519 respectively, p = 0.025) and after instillation (mean 0.552, SD 0.992 and mean 2.473, SD 1.780 respectively, p = 0.008). Both treatments were well tolerated with no statistically significant difference between the groups in the occurrence of ocular or systemic adverse events.

Administration, Topical↗
PubMed1999

A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide.

OBJECTIVE: To compare the efficacy and safety of a fixed combination of 2.0% dorzolamide and 0.5% timolol administered twice daily with each of the individual components administered in their usual monotherapy dose regimens in patients who had washed out all ocular hypotensive medications. DESIGN: A 3-month, parallel, randomized, double-masked, active-controlled, multicenter clinical trial. PARTICIPANTS: A total of 335 patients with bilateral ocular hypertension or open-angle glaucoma participated. INTERVENTION: After completing a washout of ocular hypotensive medications, patients were randomized to receive either the dorzolamide-timolol combination twice daily plus placebo once daily, 0.5% timolol twice daily plus placebo once daily, or 2.0% dorzolamide three times daily. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured at morning trough (hour 0) and peak (2 hours postdose) on day 1, week 2, and months 1, 2, and 3. Ocular and systemic safety were evaluated at each study visit. RESULTS: Intraocular pressure reduction was greater on average in the combination group than in the dorzolamide and timolol groups. At morning trough (month 3, hour 0), the mean reduction in IOP from baseline was 27.4% (-7.7 mmHg) for the combination, 15.5% (-4.6 mmHg) for dorzolamide, and 22.2% (-6.4 mmHg) for timolol. At morning peak (month 3, hour 2), the mean IOP reduction from baseline was 32.7% (-9.0 mmHg), 19.8% (-5.4 mmHg), and 22.6% (-6.3 mmHg) for the combination, dorzolamide, and timolol, respectively. Overall, the incidence of clinical adverse experiences was comparable between the combination and each of its components. The proportion of patients who discontinued from the study because of clinical adverse experiences was also comparable between the combination and dorzolamide, although it was significantly greater in the combination group than in the timolol group (7% vs. 1%, P = 0.035). Similarly, comparable numbers of patients in the combination and dorzolamide groups reported ocular symptoms; however, when compared to the timolol group, more patients receiving the combination reported blurred vision, burning eye, stinging eye, and tearing eye. CONCLUSIONS: After a washout of ocular hypotensive therapy, the IOP-lowering effect of the dorzolamide-timolol combination was greater than that of either of its components administered as monotherapy. The combination is generally well-tolerated and provides a convenient alternative to concomitant therapy with its individual components.

Adrenergic beta-Antagonists↗
PubMed1994

Combined timolol and pilocarpine vs pilocarpine alone and timolol alone in the treatment of glaucoma.

We compared the effects of pilocarpine 4% alone, timolol 0.5% alone, and a combination of timolol 0.5% and pilocarpine 4% in the treatment of glaucoma. We treated 43 patients with glaucoma using each drug and then with the combination of drugs for four weeks each. Only patients with a morning intraocular pressure of at least 24 mm Hg without treatment were included. The patients were examined, after one and four weeks of treatment with pilocarpine, timolol, or combined timolol 0.5% and pilocarpine 4%, before the morning dose and at two and five hours after it. At the end of the study, the mean reduction in intraocular pressure from baseline was 9.2 +/- 5.1 mm Hg (28.5% +/- 12.7%) with combined timolol 0.5% and pilocarpine 4%, 5.6 +/- 3.6 mm Hg (17.6% +/- 9.7%) with pilocarpine, and 7.5 +/- 5.0 mm Hg (21.2% +/- 12.6%) with timolol. Intraocular pressure was consistently lower with the combination treatment than with timolol or pilocarpine alone. We believe that this combined solution of timolol-pilocarpine is a valuable contribution to the treatment of open-angle glaucoma.

Administration, Topical↗
PubMed2004

A 12-month, multicenter, randomized, double-masked, parallel-group comparison of timolol-LA once daily and timolol maleate ophthalmic solution twice daily in the treatment of adults with glaucoma or ocular hypertension.

BACKGROUND: Timolol maleate, a nonselective beta-adrenoceptor antagonist applied topically to the eye as a solution, is well known for its ocular hypotensive efficacy. A gellan formulation of timolol maleate is given once daily and has been shown to be as effective as timolol maleate solution, but is associated with ocular symptoms that may limit its utility. A new timolol maleate solution has been formulated that contains potassium sorbate (timolol-LA [TLA; Istalol(R)]) to enhance the ocular bioavailability of timolol instilled into the eye, as well as half the benzalkonium chloride preservative found in timolol maleate. OBJECTIVE: The objective of this trial was to assess the ocular hypotensive efficacy and safety profile of TLA 0.5% solution once daily with those of timolol maleate ophthalmic solution (TIM) 0.5% twice daily in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: This multicenter, prospective, randomized, double-masked, parallel-group clinical trial was conducted at 21 participating private practices across the United States. Patients aged > or =18 years with OAG or OHT in 1 or both eyes and an unmedicated intraocular pressure (IOP) of > or =22 mm Hg were randomized to receive either TLA once daily or TIM twice daily bilaterally for 12 months. The primary outcome measure was IOP (95% CIs) on treatment difference at each visit (ie, equivalence analysis). The safety profile was assessed based on biomicroscopic and ophthalmoscopic examination and patient symptoms. RESULTS: A total of 332 patients (203 women, 129 men; mean [SEM] age, 64.6 [11.8] years [range, 29-92 years]) entered the study. Of these, 290 patients (87.3%) completed it. At none of the visits did the 95% CIs for between-treatment comparisons exceed 1.5 mm Hg and, at most of the visits, these intervals did not exceed 1.0 mm Hg. Mean baseline IOP was approximately 25 mm Hg in both groups. IOP was reduced at all posttreatment visits to 18 to 19 mm Hg at peak and to approximately 19 to 20 mm Hg at trough drug level in both treatment groups. Mean reductions from baseline were 6 to 7 mm Hg at peak and 5 to 6 mm Hg at trough (25.5%-28.7% and 20.8%-24.7%, respectively). Seventeen patients (5.1%) withdrew due to adverse events (AEs) (10 patients [6.0%] and 7 patients [4.2%] in the TLA and TIM groups, respectively). Based on biomicroscopic and ophthalmoscopic examination and volunteered symptoms, the safety profile was similar between the 2 treatments, except for burning and stinging on instillation, with an incidence of 41.6% in the TLA group and 22.9% in the TIM group (P = 0.001). Nearly all cases of burning and stinging were mild (94.2% [65 events] with TLA and 90.0% [36 events] with TIM), and none of the patients discontinued treatment due to this AE. CONCLUSIONS: TLA solution, a nonselective beta-adrenoceptor antagonist, given once daily in the morning, was found to be statistically equivalent in ocular hypotensive efficacy (as defined a priori) compared with TIM, given twice daily, and with an acceptable safety profile in this study population of adult patients.

Adult↗
PubMed1988

Ocular and cardiac beta-antagonism by timolol prodrugs, timolol and levobunolol.

Topically applied O-butyryl timolol, O-pivaloyl timolol and levobunolol (0.25 micrograms) antagonized isoproterenol-induced ocular hypotension for 8 hrs whereas timolol (0.25 micrograms) was shorter acting (4 hrs). Timolol (25 micrograms) produced greater antagonism of isoproterenol-induced tachycardia than did O-butyryl and O-pivaloyl timolol (25 micrograms). These results suggest that, at similar doses, O-butyryl and O-pivaloyl timolol produce high concentrations of timolol in ocular tissues and undergo redistribution more slowly into the systemic circulation than does topical timolol. Under certain circumstances, prodrugs may provide a mechanism for increasing selectivity and extending the duration of action in the target organ as well as decreasing systemic effects.

Adrenergic beta-Antagonists↗
PubMed1995

Evaluation of multiple doses of 4 and 6% timolol, and timolol combined with 2% pilocarpine in clinically normal beagles and beagles with glaucoma.

Topically applied 4% timolol, 4% timolol combined with 2% pilocarpine, 6% timolol, and 6% timolol combined with 2% pilocarpine were evaluated in clinically normal Beagles and Beagles with glaucoma. The drugs were instilled twice daily for 5 days. Changes in intraocular pressure (IOP), pupil size, and heart rate were recorded on days 1, 3, and 5 at 0, 2, 5, and 8 hours, starting at 8:30 AM. In clinically normal dogs, 4 and 6% topically administered timolol did not cause consistent reductions in IOP; however, with addition of 2% pilocarpine, IOP was consistently lower. In the Beagles with glaucoma, 4 and 6% timolol and, to a greater extent, 4 and 6% timolol combined with 2% pilocarpine lowered IOP. The combinations lowered IOP and reduced pupil size consistently. In all test groups, either 4 or 6% topically applied timolol caused approximately 10% decrease in mean heart rate.

Administration, Topical↗
PubMed2001

Effect of dorzolamide timolol combination versus timolol 0.5% on ocular bloodflow in patients with primary open-angle glaucoma.

PURPOSE: Addition of dorzolamide to timolol in primary open-angle glaucoma shows augmented reduction of intraocular pressure. It is unknown as yet if addition of dorzolamide will alter hemodynamics. METHODS: Fifteen patients with primary open-angle glaucoma were placed on a medication-dependent 1-week to 4-week washout that included maintenance on timolol. After washout, baseline measurements were taken (timolol). They were studied after a month on timolol or dorzolamide-timolol (Cosopt; Merck, Inc, Whitehouse Station, New Jersey), with the second drug preceded by another month of timolol maintenance and second baseline measurements. At each visit, visual function, intraocular pressure, and ocular hemodynamics were monitored, including indocyanine green and fluorescein angiography and color Doppler imaging. RESULTS: Cosopt significantly reduced intraocular pressure (14.7 to 13.4 mm Hg, P <.05) and increased arteriovenous passage time (superior temporal artery) of fluorescein dye (2.13 to 1.76 seconds, P =.01) but had no effect on visual function. CONCLUSIONS: When compared with timolol in primary open-angle glaucoma, Cosopt augments ocular tension reduction and reduces the amount of time required for blood to pass through the superior retinal vasculature.

Adrenergic beta-Antagonists↗
PubMed2003

Efficacy and safety of timolol maleate/latanoprost fixed combination versus timolol maleate and brimonidine given twice daily.

PURPOSE: To evaluate the efficacy and safety of the timolol maleate/latanoprost fixed combination (TLFC) given once each evening versus brimonidine and timolol solution given twice daily as concomitant therapy in primary open-angle glaucoma or ocular hypertension patients. METHODS: Qualified subjects were begun on timolol alone twice daily for 1 month and then randomized to either TLFC or brimonidine and timolol concomitant therapy for 6 weeks. Patients were then switched to the other treatment regimen. Intraocular pressures (IOPs) were measured every 2 hours between 08 : 00 and 20 : 00 hours at baseline and at the end of periods 1 and 2. RESULTS: This study found that in 32 subjects the IOP diurnal curve on timolol alone (20.9 +/- 2.8 mmHg) decreased to 17.9 +/- 3.2 mmHg when patients were treated with TLFC and to 19.0 +/- 2.4 mmHg when patients were treated with brimonidine and timolol (p = 0.02). Intraocular pressures at individual time-points were statistically similar between the groups at the 08 : 00 trough and 2 and 4 hours after dosing. However, beyond 4 hours after dosing, TLFC-treated subjects demonstrated a trend towards lower IOPs at each 2-hour time-point that was not statistically significant after a Bonferroni correction (p <or= 0.05). The incidence of both solicited and unsolicited side-effects was similar between groups. CONCLUSION: This study suggests that TLFC given in the evening reduces the mean daytime diurnal IOP more than brimonidine and timolol given concomitantly twice daily.

Antihypertensive Agents↗