Magnesium Hydroxide Nanoparticles Improve the Ocular Hypotensive Effect of Twice Daily Topical Timolol Maleate in Healthy Dogs.
Ontology highlight
ABSTRACT:
SUBMITTER: Kita M
PROVIDER: S-EPMC8402916 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveTo evaluate by survey the comfort upon instillation of timolol hemihydrate compared to timolol maleate with potassium sorbate.DesignA prospective, multicenter, observational, non-interventional study.ParticipantsOne hundred and three patients of open-angle glaucoma or ocular hypertension who were ≥21 years old and were currently prescribed timolol hemihydrate (once or twice daily) or timolol maleate with potassium sorbate once daily as monotherapy or as a part of two-drug therapy.Materials and methodsStudy was performed at seven clinical sites in the United States. Patients were surveyed on comfort upon instillation of timolol hemihydrate compared to timolol maleate with potassium sorbate.ResultsA difference between timolol hemihydrate and timolol maleate with potassium sorbate for questions 1 (burning/stinging on instillation, p < 0.001) and 4 (tearing on instillation, p = 0.024) was noted. There were no differences between treatment groups for any other question (p > 0.05).ConclusionThis survey suggests that timolol hemihydrate is associated with less stinging/burning and tearing than timolol maleate with potassium sorbate. How to cite this article: Stewart WC, Oehler JC, Choplin NT, Markoff JI, Moster MR, Ichhpujani P, Nelson LA. A Comfort Survey of Timolol Hemihydrate 0.5% Solution Once or Twice Daily vs Timolol Maleate in Sorbate. J Current Glau Prac 2013;7(1):11-16.
| S-EPMC4741129 | biostudies-literature
Project description:Purpose: To characterize the effects of timolol and latanoprost on calculated ocular perfusion pressure (OPP) in a multicenter, prospective, crossover-design study. Methods: Nonglaucomatous volunteers were evaluated at baseline, after 1 week of timolol 0.5% dosed twice daily, and after 1 week of latanoprost 0.005% dosed nightly (randomized treatment order; 6-week washout period). Pneumatonometric intraocular pressure (IOP) and brachial blood pressure (BP) were evaluated at each visit. Using 3 commonly used equations, OPP was calculated based on IOP and BP. The OPPs at each visit were compared by using linear mixed-effects models. Results: This analysis includes 121 participants (242 eyes; 75% female, 87% White, mean age 55 years). Mean OPP (standard deviation) calculated with mean arterial pressure was 46.8 (8.1) mmHg at baseline, 48.5 (7.9) mmHg with timolol (P = 0.005), and 49.6 mmHg (8.2) with latanoprost (P < 0.001). When compared with baseline, OPP calculated with diastolic BP was significantly increased with both timolol (1.3 mmHg) and latanoprost (3.1 mmHg). The OPP calculated with systolic BP was increased with latanoprost (2.8 mmHg) but decreased with timolol (-1.3 mmHg). Timolol reduced systolic BP by 3.2 mmHg. Compared with timolol, latanoprost conferred greater increases in OPP calculated with both systolic and diastolic BP compared with baseline; however, the difference in treatment effects on OPP calculated with mean arterial pressure was not significantly different (P = 0.068). Conclusion: In this crossover study of nonglaucomatous volunteers, latanoprost increased OPP. However, timolol's benefit to OPP may be limited in part because it reduced systolic BP. Clinical Trial Registration number: NCT01677507.
| S-EPMC8713568 | biostudies-literature
Project description:Purpose. To evaluate the safety and efficacy of adding brinzolamide 1%/timolol maleate 0.5% fixed combination (BTFC) to a prostaglandin analog (PGA). Methods. This was a 12-week, open-label, single-arm study of patients with open-angle glaucoma or ocular hypertension with intraocular pressure (IOP) not sufficiently controlled after ?4 weeks of PGA monotherapy. The primary outcome was mean IOP change from baseline at week 12. Other outcomes included IOP change from baseline at week 4, percentage of patients achieving IOP ?18?mmHg at week 12, and patient experience survey responses at week 12. Results. Forty-seven patients were enrolled and received treatment. The most commonly used PGAs were latanoprost (47%) and travoprost (32%). Mean ± SD IOP was decreased at week 12 (17.2 ± 4.1?mmHg) compared with baseline (23.1 ± 3.0?mmHg; P < 0.001, paired t-test); IOP at week 4 was 17.2 ± 3.3?mmHg. At week 12, 70% of patients achieved IOP ?18?mmHg. Patient-reported symptoms (e.g., pain and redness) were mostly unchanged from baseline. Twenty-eight adverse events (AEs) were reported; the most frequently reported AE was headache (3 events in 2 patients). Conclusion. Adjunctive BTFC + PGA therapy was effective and well tolerated. IOP decreased by 6?mmHg at weeks 4 and 12.
| S-EPMC4606181 | biostudies-literature
Project description:ImportanceOral β-blockers used for the prevention of migraine headache are not effective for the treatment of acute pain. Small case series have suggested that topically applied β-blockers may be useful in the management of acute migraine pain, warranting evaluation with randomized clinical trials.ObjectiveTo evaluate the short-term efficacy and safety of topically applied timolol maleate ophthalmic solution, 0.5%, compared with topically applied placebo eyedrops in the treatment of acute migraine attacks.Design, setting, and participantsIn this randomized, masked placebo-controlled crossover trial conducted from May 27, 2015, to August 28, 2017, 50 patients with migraine were randomized to receive either timolol eyedrops, 0.5%, or a placebo eyedrop (carboxymethyl cellulose, 0.5%). After a 3-month treatment period, patients completed a 1-month washout period and were crossed over to receive the opposite treatment for a final 3 months. Analysis was performed on a modified intent-to-treat basis.InterventionAfter random assignment, patients were instructed to use 1 drop of the assigned medication in each eye at the earliest onset of migraine.Main outcomes and measuresThe main outcome measure was reduction in pain score with treatment. The primary end point was reduction of pain score by 4 points, or to zero, 20 minutes after instillation of the eyedrop.ResultsOf the 50 patients, 42 (84%) were females and the mean (SD) age was 27.3 (11.3) years. Of a total of 619 migraine attacks, 284 (46%) were treated with timolol, 271 (44%) were treated with the placebo, and 64 (10%) occurred during the washout period when no study medications were used. Seven patients (14%) withdrew after randomization. A total of 233 of the timolol-treated migraine attacks (82%) were associated with a reduction in pain score by 4 points, or to zero, at 20 minutes compared with 38 of the placebo-treated attacks (14%), with a difference of 68 percentage points (95% CI, 62-74 percentage points). A generalized estimating equation analysis revealed that pain score reduction at 20 minutes was greater in the timolol group compared with the placebo group by a mean (SE) of 4.63 points (0.34) (P < .001).Conclusions and relevanceThis randomized crossover trial supports consideration of timolol eyedrops in the acute treatment of migraine. Further research is warranted to determine if the improvements observed are sustained for a longer follow-up and with larger groups.Trial registrationCTRI/2015/05/005829, UTN: U1111-1167-6439.
| S-EPMC7530820 | biostudies-literature
Project description:AimTo evaluate whether latanoprost/timolol fixed combination (LTFC) dosed twice daily may provide further intraocular pressure (IOP) reduction and evaluate the safety profile at this dose.MethodsThis is an open-labeled, randomized, prospective crossover study on fourty primary open angle glaucoma patients. Two weeks of washout period were followed by randomization to either once daily (OD, group A) or twice daily dosing (BD, group B) of LTFC for 4wk. After another 2-week washout period, the patients' treatment dose was crossed-over for another 4wk. IOP reduction alongside ocular and systemic side effects were evaluated.ResultsMean baseline IOP was 18.57±2.93 and 17.8±3.01 mm Hg before OD and BD dose respectively, (P=0.27). Mean IOP after BD dose was statistically lower (12.49±1.59 mm Hg) compared to OD (13.48±1.81 mm Hg, P=0.017). Although IOP reduction after BD dose was more (5.32±3.24 mm Hg, 29.89%) than after OD dosing (5.04 mm Hg, 27.14%), it did not reach statistical significance (P=0.68). Patients switched from OD to BD (group A) showed mean IOP reduction by 0.69 mm Hg [95% confidence interval (CI): -0.09 to 1.48 mm Hg, P=0.078]; but patients switched from BD to OD (group B) had significantly higher mean IOP by 1.25 mm Hg (95%CI: -2.04 to -0.46 mm Hg, P=0.006). BD dose had more ocular side effects albeit mild.ConclusionMean IOP after LTFC dosed twice daily is statistically lower, with additional mild side effects.
| S-EPMC10398532 | biostudies-literature
Project description:Acne is a common inflammatory condition that mostly involves the face, chest and back. A number of different modalities had been employed for treating scars of which laser remains to be a pivotal choice. We aimed to compare the efficacy of topical timolol maleate 0.5% after fractional CO2 (AFCO2) laser versus fractional CO2 Laser alone for treatment of atrophic acne scars. A split-face comparative clinical experiment on 30 cases of atrophic post-acne scars that were treated on one side with ablative fractional CO2 laser followed by timolol application while with only ablative fractional CO2 laser on the other side. Following treatment, both sides demonstrated significant improvement with the laser + timolol treated side showing better improvement; yet not significantly higher than the laser only treated side. In conclusion, both topical timolol maleate 0.5% after fractional CO2 laser and fractional CO2 laser may achieve comparable significant improvement. The good safety profile, easy accessibility, low cost, and non-invasive nature merits the use of timolol in acne scars pending verification by larger sample reproduced and controlled trials.
| S-EPMC10256714 | biostudies-literature
Project description:PurposeMedical treatment of glaucoma relies on intraocular pressure (IOP)-lowering medications, typically administered daily by the patient. While these medications are effective when applied correctly, patient adherence is a major obstacle in glaucoma treatment. We have developed a sustained-release formulation of timolol maleate that can be injected subconjunctivally to avoid patient noncompliance.MethodsA biodegradable microsphere formulation for timolol maleate was injected subconjunctivally in normal rabbits. We measured timolol levels in tears, aqueous humor, vitreous humor, and serum of study rabbits. Furthermore, IOP profiles were recorded longitudinally. Tissue compatibility and side effects were evaluated using histochemistry.ResultsThe microsphere formulation led to measureable amounts of timolol in the aqueous humor and the tear film for up to 90 days. Timolol was not detectable in the serum at any time. A significant reduction of IOP was observed in treated eyes. Clinically, the subconjunctival administration of the microspheres was well tolerated with no signs of inflammation or infection. The absence of local inflammation was confirmed by histology.ConclusionsA single subconjunctival administration of timolol microspheres achieved delivery and IOP reduction in rabbits for up to 90 days without local or systemic inflammation or toxicity. This approach has the potential to improve the management of glaucoma in patient populations, who are challenged to adhere to a regimen of daily eye drops.
| S-EPMC5165680 | biostudies-literature
Project description:IntroductionThe efficacy of lowering intraocular pressure (IOP) and safety of switching to travoprost/timolol fixed combination ophthalmic solution (Duotrav(®), Alcon Laboratories, Inc., Fort Worth, TX, USA) in patients with primary open-angle glaucoma, normal tension glaucoma or ocular hypertension undergoing prostaglandin analog (PGA) monotherapy was investigated.MethodsPatients treated with travoprost, latanoprost, tafluprost, or bimatoprost for ≥3 months and requiring additional medication were switched to Duotrav without washout. Baseline IOP was calculated from measurements at two visits during PGA monotherapy. IOP reductions at 4, 8, and 12 weeks after switching to Duotrav and adverse events were assessed.ResultsOf 162 patients enrolled, 157 patients (96.9%) with ≥4 weeks of follow-up after switching to Duotrav were analyzed. The mean IOP decreased significantly (baseline = 16.3 ± 3.1 mmHg; 4 weeks = 14.6 ± 3.1 mmHg, 8 weeks = 14.7 ± 3.3 mmHg, 12 weeks = 14.6 ± 3.2 mmHg; all P < 0.0001). When study eyes were divided into three groups according to baseline IOP (≥19 mmHg: 33 eyes, 21.0%; ≥15 to <19 mmHg: 78 eyes, 49.7%; <15 mmHg: 46 eyes, 29.3%), all groups showed significant IOP reductions (P = 0.0324 ~ P < 0.0001) after switching to Duotrav. Twenty-seven of 166 patients (16.3%) in the safety analysis experienced adverse events and 26/166 patients (15.7%) experienced adverse events, for which a relationship to Duotrav could not be ruled out. Adverse events in five patients led to treatment discontinuation (eye pruritus; eye irritation; increased blood pressure and rash; increased blurred vision; deepening of the eyelid sulcus and blepharoptosis). Twelve weeks after treatment switching, eyelash changes, blepharal pigmentation and deepening of the eyelid sulcus occurred in 42 (26.8%), 29 (18.5%), and 13 (8.3%) cases, respectively, among 157 patients with follow-up. There was no significant worsening from baseline for superficial punctate keratopathy (SPK) or conjunctival hyperemia after switching (SPK score: baseline = 0.58 ± 1.31; 12 weeks = 0.92 ± 1.76, P = 0.1819; conjunctival hyperemia score: baseline = 0.41 ± 0.64; 12 weeks = 0.49 ± 0.63, P = 0.3774).ConclusionOur findings confirm that switching to Duotrav(®) in PGA monotherapy patients shows IOP-lowering effect with minimal safety concerns.FundingJapan Association of Health Service and Alcon Japan. Ltd.Trial registrationUMIN Clinical Trials Registry identifier, UMIN000007028.
| S-EPMC4604505 | biostudies-literature
Project description:PurposeTo investigate the therapeutic effects of eye drops, namely, timolol maleate, a β-adrenergic receptor antagonist, and latanoprost, a prostaglandin F2α analog, on retinal edema in a murine retinal vein occlusion (RVO) model.MethodsAn RVO model was established using laser-induced RVO in mice, which were administered timolol maleate and latanoprost eye drops several times after venous occlusion. Subsequently, the thickness of the inner nuclear layer (INL) and the expression levels of such genes as Vegf and Atf4, which are stress markers of the endoplasmic reticulum, were examined. Primary human cultured retinal microvascular endothelial cells (HRMECs) were treated with timolol under hypoxic conditions, after which the gene expression pattern was investigated. Importantly, an integrated stress response inhibitor (ISRIB) was used in the RVO model, he known ISRIB, which suppresses the expression of ATF4 in retinal edema.ResultsIncreased INL thickness was suppressed by timolol eye drops, as were the expressions of Vegf and Atf4, in the RVO model. However, latanoprost eye drops did not induce any change in INL thickness. In HRMECs, hypoxic stress and serum deprivation increased the Vegf and Atf4 expressions; in response, treatment with timolol suppressed the Vegf expression. Furthermore, the ISRIB decreased the Vegf expression pattern and edema formation, which are associated with RVO.ConclusionsThese results indicate that timolol eye drops may be a potential option for RVO treatment.
| S-EPMC10784217 | biostudies-literature
Project description:Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed.New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve.Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6-8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation.Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties), formulations of bimatoprost 0.01% can be administered once or twice daily. These findings support development of bimatoprost 0.01%-based fixed-dose combination therapies administered twice daily for patients who require multiple adjunctive medications to control their IOP.
| S-EPMC5627754 | biostudies-other