C17H25NO3.HCl
C17H26ClNO3
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InChI=1S/C17H25NO3.ClH/c1-17(2,3)18-10-12(19)11-21-16-9-5-6-13-14(16)7-4-8-15(13)20;/h5-6,9,12,18-19H,4,7-8,10-11H2,1-3H3;1H/t12-;/m0./s1 |
DNTDOBSIBZKFCP-YDALLXLXSA-N |
Cl.CC(C)(C)NC[C@H](O)COc1cccc2C(=O)CCCc12 |
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beta-adrenergic antagonist
An agent that binds to but does not activate beta-adrenergic receptors thereby blocking the actions of endogenous or exogenous beta-adrenergic agonists. beta-Adrenergic antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches and anxiety.
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beta-adrenergic antagonist
An agent that binds to but does not activate beta-adrenergic receptors thereby blocking the actions of endogenous or exogenous beta-adrenergic agonists. beta-Adrenergic antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches and anxiety.
antiglaucoma drug
Any drug which can be used to prevent or alleviate glaucoma, a disease in which the optic nerve is damaged, resulting in progressive, irreversible loss of vision. It is often, though not always, associated with increased pressure of the fluid in the eye.
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View more via ChEBI Ontology
5-[(2S)-3-(tert-butylamino)-2-hydroxypropoxy]-3,4-dihydronaphthalen-1(2H)-one hydrochloride
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(−)-3,4-dihydro-5-(3-(tert-butylamino)-2-hydroxypropoxy)-1(2H)-naphthalenone hydrochloride
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ChemIDplus
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(−)-5-(3-(tert-butylamino)-2-hydroxypropoxy)-3,4-dihydro-1(2H)-naphthalenone hydrochloride
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ChemIDplus
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(2S)-N-(tert-butyl)-2-hydroxy-3-[(5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)oxy]propan-1-aminium chloride
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IUPAC
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levobunolol HCl
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ChemIDplus
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levobunolol hydrochloride
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KEGG COMPOUND
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levobunolol monohydrochloride
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ChEBI
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27912-14-7
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CAS Registry Number
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ChemIDplus
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Baker MM, Belal TS (2018) Validated HPLC-DAD Method for the Simultaneous Determination of Six Selected Drugs Used in the Treatment of Glaucoma. Journal of AOAC International 101, 993-1000 [PubMed:28859698] [show Abstract] This work presents a simple, sensitive, and generic HPLC-diode-array detection method for the simultaneous determination of six drugs prescribed for the treatment of open-angle glaucoma and ocular hypertension. The investigated drugs include brimonidine tartarate (BMN), acetazolamide (AZA), brinzomaide (BZA), dorzolamide HCl (DZA), levobunolol HCl (LVB), and timolol maleate (TIM). Efficient chromatographic separation was achieved using a Thermo Hypersil BDS C18 column (4.6 × 250 mm, 5 µm) with a mobile phase consisting of phosphate buffer pH 5 and acetonitrile in a ratio of 78 + 22. The flow rate was 1 mL/min, and quantification was based on measuring peak areas at 298 nm for TIM and 254 nm for the other drugs. Peaks were perfectly resolved, with retention times at 3.06, 3.87, 4.53, 5.78, 7.31, and 10.78 min for BMN, AZA, DZA, TIM, LVB, and BZA respectively. The developed method was validated according to International Conference on Harmonization guidelines with respect to system suitability, linearity, ranges, accuracy, precision, robustness, and LODs and LOQs. The proposed method showed good linearity in the ranges of 2-80, 2.5-100, 2.5-100, 5-200, 3.75-150, and 1.75-70 µg/mL for BMN, AZA, DZA, TIM, LVB, and BZA, respectively. LODs were 0.20-1.01 μg/mL for the analyzed compounds. Applicability of the proposed method to real-life situations was assessed through the analysis of five different pharmaceutical formulations, and satisfactory results were obtained. | Lin L, Wang Y, Chen Y, Liu M (2014) Bradyarrhythmias secondary to topical levobunolol hydrochloride solution. Clinical interventions in aging 9, 1741-1745 [PubMed:25342892] [show Abstract] An 88-year-old man was admitted with fatigue, dizziness, and heart palpitations. Both the electrocardiogram and Holter confirmed the existence of sinus bradycardia and sinus arrest. One hour prior to the onset of symptoms, he received levobunolol hydrochloride solution topically. The levobunolol hydrochloride solution was discontinued and the bradycardia resolved. He was diagnosed as having intermittent sinus bradycardia and sinus arrest, induced by topical β-blocker therapy. Levobunolol hydrochloride solution is an effective therapy for ocular hypertension, probably by reducing aqueous fluid production. However, it can induce cardiac side effects such as bradyarrhythmia and should be used with caution in elderly patients or patients with cardiac disease. | Karataş A, Sonakin O, Kiliçarslan M, Baykara T (2009) Poly (epsilon-caprolactone) microparticles containing Levobunolol HCl prepared by a multiple emulsion (W/O/W) solvent evaporation technique: effects of some formulation parameters on microparticle characteristics. Journal of microencapsulation 26, 63-74 [PubMed:18608798] [show Abstract] The aim of this study was to prepare poly (epsilon-caprolactone) (PCL) microparticles of Levobunolol HC1 (L-HC1) for use as an anti-glaucomatous drug to the eye. The double emulsion (W/O/W) solvent evaporation technique was used for encapsulating L-HC1 as a hydrophilic drug. The study examined the impact of different factors including the pH and volume of the external aqueous phase, the concentration of polyvinylalcohol (PVA) and Pluronic F68 (PF68) used as stabilizers and drug/polymer ratios on the characteristics of the microparticles. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were used to identify the physical state of the drug and polymer. The zeta potential of the particles was also identified. Entrapment efficiency was found to be highest with a 0.5% PVA concentration and 100 mL volume of external aqueous phase at pH 12. The high efficiency was due to a reduction in the degree of drug ionization. The microparticles were spherical and appropriately sized for ophthalmic application. Drug release from the microparticles appears to consist of two components, with an initial rapid release followed by a slower stage. Drug release was slower when the microparticle was incorporated into the thermally reversible gel (Pluronic F127) in comparison to drug release from the free drug incorporated into the gel and drug release from the free microparticle. | Ramadan NK, Zaazaa HE (2007) Membrane electrodes for determination of some beta-blocker drugs. Journal of AOAC International 90, 987-994 [PubMed:17760336] [show Abstract] Five poly(vinyl chloride) (PVC) matrix membrane electrodes responsive to the beta-blockers atenolol (AT), bisoprolol fumarate (BI), timolol maleate (TI), and levobunolol HCl (LV) were developed and characterized. A precipitation-based technique with ammonium reineckate anion as an electroactive material in PVC matrix with AT, BI, TI, and LV cations was used for fabrication of Electrodes 1-4, respectively. Electrode 5 fabrication was based on precipitation of LV cation with tungstophosphate anion as an electroactive material. Fast and stable Nernstian responses at 1 x 10(-2)-1 x 10(-7) M for different beta-blockers over the pH range of 2-8 were found for these electrodes, which were evaluated according to International Union of Pure and Applied Chemistry recommendations. The method was successively applied for the determination of beta-blockers in their pharmaceutical formulations. Validation of the method according to quality assurance standards showed the suitability of the proposed electrodes for use in the quality control assessment of these drugs. The recoveries for the determination of the beta-blocker drugs by the 5 proposed selective electrodes were 100.1 +/- 0.7, 99.9 +/- 0.8, 100.0 +/-1.1, 100.5 +/- 1.1, and 100.6 +/- 0.7% for Sensors 1-5, respectively. Statistical comparison between the results obtained by this method and the official method of the drugs was performed and no significant difference was found. | Ishibashi T, Yokoi N, Kinoshita S (2003) Comparison of the effects of topical levobunolol and timolol solution on the human ocular surface. Cornea 22, 709-715 [PubMed:14576520] [show Abstract]
PurposeTo compare the effects of levobunolol hydrochloride and timolol maleate on tear volume, precorneal tear film stability, and corneal epithelial barrier function in normal human eyes.Subjects and methodsThe study population consisted of 14 healthy volunteers. To obtain pretreatment baseline values, we determined the radius of the tear meniscus (RTM) by meniscometry; the noninvasive breakup time (NIBUT) of the precorneal tear film with a tear specular microscope; and corneal fluorescein uptake with a fluorophotometer. Levobunolol hydrochloride (0.5%) or timolol maleate solution (0.5%) was instilled twice daily for 4 weeks into 1 eye; the contralateral eye was treated with the other topical drug twice daily for the same period. At the end of the study period, the same tests were performed, and the pre- and posttreatment results were compared.ResultsTimolol solution did, and levobunolol did not, significantly reduce NIBUT from the baseline values. RTM was significantly decreased by treatment with either timolol or levobunolol solution. Corneal fluorescein uptake was not significantly changed, although it was higher after treatment with both topical drugs.ConclusionsFour-week treatment with timolol solution resulted in significant instability of the precorneal tear film. Both timolol and levobunolol solution significantly decreased tear volume on the ocular surface. These results indicate that levobunolol solution applied twice daily has equal effects on the tear volume and corneal epithelial barrier function as does timolol solution applied twice daily and that it affects precorneal tear film stability less than timolol solution. | Halper LK, Johnson-Pratt L, Dobbins T, Hartenbaum D (2002) A comparison of the efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD and 0.5% levobunolol hydrochloride BID in patients with ocular hypertension or open-angle glaucoma. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 18, 105-113 [PubMed:12002664] [show Abstract] The purpose of this study was to compare the ocular hypotensive efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution (timolol gel) and 0.5% levobunolol hydrochloride (levobunolol). This was a randomized, double-masked, multi-center, active-controlled, 2-period, crossover study. After a 3-week, single-masked placebo run-in phase, patients with ocular hypertension or open-angle glaucoma and an intraocular pressure (IOP) > or = 22 mmHg were randomized to receive timolol gel QD or levobunolol BID for 6 weeks followed by a 3-week, placebo washout period. Patients were then crossed over to the alternate treatment for 6 weeks. IOP and heart rate (HR) were measured at 3 and 6 weeks after the start of therapy with either timolol gel or levobunolol. Of 133 patients randomized, 116 received both treatments. Timolol gel QD was comparable to levobunolol BID in reducing trough and peak IOP. At trough, HR was marginally increased with timolol gel and was decreased with levobunolol (p = < 0.001). At peak, HR was decreased with both treatments, but the decrease was significantly less with timolol gel than with levobunolol (p = 0.049). Significantly more patients experienced at least one adverse event (p = 0.024), adverse events related to special senses (p = 0.002), and burning and stinging (p < 0.001) with levobunolol compared to timolol gel. The study demonstrates that timolol gel QD has IOP-lowering effects comparable to those of levobunolol BID with fewer adverse experiences and less effect on HR. | Vold SD, Wiggins DA, Jackimiec J (2000) Cost analysis of glaucoma medications. Journal of glaucoma 9, 150-153 [PubMed:10782624] [show Abstract]
PurposeTo evaluate the yearly cost in 1998 of glaucoma medications to patients and to the Health Plan at a university-affiliated teaching hospital with its own health maintenance organization.Materials and methodsData concerning Health Plan glaucoma-medication prescriptions for 1998 were retrieved from the hospital pharmacy database.ResultsThe most costly medication per patient per year was latanoprost (Xalatan; Pharmacia & Upjohn, Kalamazoo, MI [$337]), followed by betaxolol hydrochloride (Betoptic-S; Alcon, Fort Worth, TX [$336]), dorzolamide (Trusopt; Merck & Co., West Point, PA [$288]), brimonidine tartrate (Alphagan; Allergan Pharmaceuticals, Irvine, CA [$260]), timolol maleate 0.5% in a gel-forming solution (Timoptic-XE 0.5%; Merck & Co., West Point, PA [$199]), levobunolol hydrochloride (Betagan; Allergan Pharmaceuticals, Irvine, CA [$195]), and generic timolol maleate 0.5% ($132). Cost per unit was greatest for Betoptic-S ($51), exceeding that of Trusopt ($43) and Xalatan ($43), Alphagan ($42), Betagan ($38), Timoptic-XE 0.5% ($32), and timolol maleate 0.5% ($27).ConclusionVariability in the cost of medications may influence the long-term medical management of glaucoma patients. | Walters TR, Maloney S, Slater D, Liss C, Wilson H, Hartenbaum D (1998) Efficacy and tolerability of 0.5% timolol maleate ophthalmic gel-forming solution QD compared with 0.5% levobunolol hydrochloride BID in patients with open-angle glaucoma or ocular hypertension. Clinical therapeutics 20, 1170-1178 [PubMed:9916610] [show Abstract] We compared the efficacy of timolol maleate ophthalmic gel-forming solution 0.5% QD with that of levobunolol hydrochloride 0.5% BID, as measured by change in intraocular pressure (IOP), effect on heart rate, and ocular tolerability. The study had a positive-controlled, double-masked, randomized, multicenter, 12-week, two-period (6 weeks each), crossover design. One hundred fifty-two patients with open-angle glaucoma or ocular hypertension were randomized to receive either timolol maleate gel-forming solution QD or levobunolol BID for 6 weeks, followed by a crossover to the alternate treatment. IOP and heart rate were measured at morning trough and peak during weeks 3, 6, 9, and 12. Timolol maleate gel-forming solution QD was comparable to levobunolol BID in reducing IOP at peak and trough. Although the effects on peak heart rate were similar between the two medications, the effect on trough heart rate of timolol maleate gel-forming solution QD was significantly less than that of levobunolol BID (P = 0.001). The incidence of ocular burning and stinging was comparable between the two treatments. Patients experienced significantly more blurred vision when using timolol maleate gel-forming solution than when using levobunolol (P = 0.013). Overall, more patients experienced at least one adverse event when using timolol maleate gel-forming solution. Timolol maleate gel-forming solution QD is as efficacious in reducing IOP as levobunolol BID. | Bloom AH, Grunwald JE, DuPont JC (1997) Effect of one week of levobunolol HCl 0.5% on the human retinal circulation. Current eye research 16, 191-196 [PubMed:9088734] [show Abstract]
PurposeTo determine the effect of one week of topical treatment with levobunolol HCl 0.5% on the retinal circulation of normal subjects.MethodsFifteen healthy volunteers with no history of ocular disease were included in this study. In a double-masked, randomized, cross-over design, one eye of each subject was treated, for one week, with one drop of either levobunolol or placebo, administered twice daily. Following a washout period of at least three weeks, the same eye received the alternate treatment for one week. Before the beginning of therapy and then two hours after the last drop, vessel diameter (D), maximum erythrocyte velocity (Vmax), and volumetric blood flow rate (Q) were determined in one major retinal vein of the treated eye, using bidirectional laser Doppler velocimetry and monochromatic fundus photography. Statistical analysis was performed using two-tailed, paired Student's t-test, linear regression, and correlation analysis.ResultsThe average percentage change from baseline in intraocular pressure was statistically significant following levobunolol (-15% +/- 13% (+/-1 SD), P < .001), but not following placebo (-3% +/- 11%, P > .05). No significant changes in average D, Vmax, or Q were observed after levobunolol treatment (-1% +/- 4%, 5% +/- 11%, 4% +/- 15%, respectively) or placebo treatment (-1% +/- 4%, -2% +/- 9%, -5% +/- 10%, respectively). The average difference between the changes in Q from baseline after levobunolol and placebo treatments (9% +/- 17%) achieved a significance level of P = 0.06. Furthermore, following levobunolol treatment, Q was 7% +/- 14% higher than following placebo treatment (P = 0.05).ConclusionsA comparison of the effects of placebo and levobunolol treatments suggests that levobunolol has a variable effect on the retinal circulation with a tendency to show an overall slight increase in flow. | Leung M, Grunwald JE (1997) Short-term effects of topical levobunolol on the human retinal circulation. Eye (London, England) 11 ( Pt 3), 371-376 [PubMed:9373479] [show Abstract]
PurposeThe effect of topical levobunolol HCl 0.5% on the retinal circulation was studied on 15 normal volunteers aged 21-54 years (32 +/- 10 years).MethodsIn a double-masked, randomised design, one eye of each subject received a drop of levobunolol HCl 0.5% (LEV) and the fellow eye received a drop of artificial tears (TEAR). Leucocyte velocity (VBFS) and density in the retinal macular microcirculation were measured by the blue-field simulation technique. Venous diameter (D), maximum erythrocyte velocity (Vmax) and volumetric blood flow rate (Q) were measured in a major temporal vein by laser Doppler velocimetry and monochromatic fundus photography.ResultsThe following average changes from baseline were observed 2 hours after treatment: heart rate, -4.6 +/- 8.3% (p = 0.04); intraocular pressure, -31.7 +/- 10.6% (p = 0.0001); and perfusion pressure, 15.4 +/- 14.4% (p = 0.02) in LEV eyes; no statistically significant changes in IOP and perfusion pressure were seen in TEAR eyes. When each eye was compared with its own baseline, there were no significant changes in VBFS, density, D, Vmax and Q in LEV eyes. In TEAR eyes, there were no significant changes in VBFS, density, Vmax and Q, but a significant change in D (-1.8 +/- 2.6%; p = 0.02) was observed. A significant average percentage increase in Q of 10.9 +/- 19.2% (paired t-test between the change after LEV and the change after TEAR, p = 0.044) was seen in LEV eyes when compared with TEAR eyes. Twelve of the 15 subjects demonstrated a relative increase in Q in the LEV eyes in comparison with the TEAR eyes, while 3 subjects showed the opposite.ConclusionA significant difference in the effect of levobunolol between the two eyes was detected, even though there was no statistically significant effect when each eye was compared with its baseline. | Tang M, Chen L, Wei W, Yang L, Wang T, Liu Z, Hu X, Sun H, Luo H (1997) The effect of levobunolol hydrochloride on the calcium and potassium channels in isolated ventricular myocytes of guinea pig. Journal of Tongji Medical University = Tong ji yi ke da xue xue bao 17, 90-93 [PubMed:9639797] [show Abstract] The effects of levobunolol hydrochlorid (Bun) on the type L calcium channel currents (ICA) and delayed rectifier potassium channel currents (IK) in isolated ventricular myocytes of guinea pig were studied by using patch clamp whole cell recording techniques. The results were showed that: 1) Bun caused a dose dependent decrease in ICA and a dose-dependent increase in IK of the ventricular myocytes. The threshold concentrations of Bun for ICA and IK were 10(-8) mol/L and 10(-7) mol/L respectively. The maximum effective concentration of Bun for bot ICA and IK was 3x10(-5) mol/L, and half-maximal concentration was 3x10(-6) mol/L; 2) IK was blocked by 2x100(-6) mol/L tetraethylammonium (TEA). A concentration of 3x10(-6) mol/L Bun showed a decreasing effect on the ICA as revealed by the current-voltage relationship curve, i.e., Bun caused an elevation of the curve;3) When ICA was blocked by 2x10(-6) mol/L Isoptin (Verapamil), at a concentration of 3x10(-6) mol/L Bun showed an increasing effect on IK and the effect could be blocked by TEA. The above-mentioned results indicated that Bun had an inhibitory effect on ICA and a fascilitatory effect on IK. The results suggested that the molecular mechanisms of antihypertensive, heart rate slowing the beta -receptor blocking effects of Bun might be due to decrease of ICA and increase of IK. | Hyung SM, Kim DM, Hong C, Lee J, Youn DH (1994) Effects of postoperative mitomycin C on glaucoma filtration surgery in rabbits treated preoperatively with antiglaucoma medications. Ophthalmic surgery 25, 704-714 [PubMed:7898865] [show Abstract] In a rabbit model, we evaluated the effects of topically applied postoperative mitomycin C (MMC) on the success rate of glaucoma filtration surgery in animals treated preoperatively with pilocarpine hydrochloride 4% and levobunolol hydrochloride (Betagan) for 16 weeks. Full-thickness filtration surgery was performed with a single 5-minute intraoperative exposure to a sponge soaked with 0.4 mg/mL MMC of one eye in nine rabbits in one group (group A) and to both eyes in 13 rabbits in a second group (group B). In addition, one eye of each rabbit in group B received a daily drop of 0.4 mg/mL MMC for 13 days after the operation. All of the eyes were then followed for 80 days. The intraoperatively applied MMC enhanced the success rate of the filtration surgery in the group A eyes. However, the eyes that also received postoperative drops of MMC (group B) had longer periods of reduced intraocular pressure (IOP) (P [chi-squared = 5.94] < .025), fewer bleb failures (P [chi-squared = 8.09] < .005), and more complications than the eyes that received only intraoperative MMC. | Stubbs GM (1994) Betagan drops. The Medical journal of Australia 161, 576 [PubMed:7968772] | Síp L, Růzicková E (1992) [Levobunolol HCl--a beta-blocker produced by the firm Allergan]. Ceskoslovenska oftalmologie 48, 370-373 [PubMed:1486629] [show Abstract] Vistagan is a new beta-blocker produced by Allergan that is used for treatment of glaucoma. The results of a clinical trial with 18 patients with open-angle glaucoma, previously treated with Timoptol, are presented. Vistagan was as effective as Timoptol in reducing the intraocular pressure and was better tolerated by patients. | Fry LL (1992) Comparison of the postoperative intraocular pressure with Betagan, Betoptic, Timoptic, Iopidine, Diamox, Pilopine Gel, and Miostat. Journal of cataract and refractive surgery 18, 14-19 [PubMed:1346539] [show Abstract] A randomized, masked study measuring postoperative intraocular pressure at 4, 8, and 24 hours, two to seven days, and one month after planned extracapsular cataract extraction with posterior chamber lens implantation was conducted. Seven commonly used ocular hypotensive agents and a control, given at the completion of surgery, were compared: timolol maleate (Timoptic), levobunolol hydrochloride (Betagan), betaxolol hydrochloride (Betoptic), pilocarpine hydrochloride (Pilopine Gel), carbachol (Miostat), apraclonidine hydrochloride (Iopidine), acetazolamide (Diamox). There were significant differences between agents. Miostat was the most effective in controlling postoperative IOP, followed by Timoptic. Diamox, Pilopine Gel, and Betagan were equally effective. Betoptic was somewhat less effective and Iopidine was not significantly better than the control. | Derick RJ, Robin AL, Tielsch J, Wexler JL, Kelley EP, Stoecker JF, Novack GD, Coleman AL (1992) Once-daily versus twice-daily levobunolol (0.5%) therapy. A crossover study. Ophthalmology 99, 424-429 [PubMed:1565455] [show Abstract] The authors executed a two-period, randomized, double-masked, crossover study comparing once-daily to twice-daily levobunolol hydrochloride (0.5%) in 20 patients with elevated intraocular pressure (IOP). Modified diurnal curves were performed at four times for each study arm: baseline, day 1, day 14, and day 28. The mean diurnal corrected decrease in IOP from baseline ranged from 16% +/- 11% to 22% +/- 9% when the subjects were treated twice daily, and from 14% +/- 10% to 18% +/- 8% when the same subjects were treated once daily. At day 1, patients had a significantly greater IOP lowering after twice-daily therapy than after once-daily therapy (P less than 0.05). At 14 and 28 days, there was no clinically significant difference between the two treatment regimens. The results of our crossover study suggest that once-daily treatment with levobunolol (0.5%) is as effective as twice-daily treatment. | Egorov EA, Shmeleva IA (1992) [Results of the clinical study of a new adrenergic beta blocker levobunolol hydrochloride in healthy subjects and in patients with glaucoma]. Vestnik oftalmologii 108, 24-25 [PubMed:1481323] [show Abstract] Effects of a single instillation of levobunolol, a new nonselective beta-adrenoblocker, in normal subjects and patients with various forms of glaucoma were under study, as were the effects of prolonged administration of this drug in patients with open-angle glaucoma. Short-term observations have revealed a hypotensive effect in all the examinees, the highest in patients with open-angle glaucoma (30.2%). Levobunolol did not influence the diameter of the pupil and accommodation, nor did it essentially change the cardiovascular activity. Prolonged administration of the drug resulted in a stable reduction of intraocular pressure by 20-30% in 70% of patients with open-angle glaucoma. Tonographic studies have shown that the drug reduced the intraocular fluid production and in case of a prolonged administration a trend to an elevation of the coefficient of the easiness of fluid discharge is observed. | Follmann P, Varga M, Daróczy J (1989) The effect of timolol, betaxolol and levobunolol on the surface of rabbit cornea. International ophthalmology 13, 81-84 [PubMed:2663750] [show Abstract] Pigmented rabbits were treated with timolol maleate, betaxolol hydrochloride or levobunolol hydrochloride eye drops twice a day for six months. Animals of the same age group and breed were used as controls. There were no differences observed in corneal epithelium with light and transmission electron microscopy. With scanning electron microscopy, in the timolol and betaxolol treated animals the picture of the corneal surface was similar to that of normal rabbit corneas after exposure to air. In scanning electron micrographs of the levobunolol treated animals, the corneal surface resembled the corneas of normal rabbits treated with artificial tears. | Liu GS, Trope GE, Basu PK (1989) Ultrastructural effects of topical betoptic, betagan, and timoptic on the rabbit corneal endothelium. Journal of ocular pharmacology 5, 329-342 [PubMed:2628505] [show Abstract] Scanning and transmission electron microscopy was used to evaluate the cytotoxic effect of three commercially available beta adrenergic blockers (Betoptic 0.5%, Betagan 0.5% and Timoptic 0.5%), and preservative (benzalkonium chloride 0.01%) on rabbit corneal endothelium. Evaluation was performed on groups including intact corneas, de-epithelialized corneas, full-thickness corneal grafts with intact epithelium, and de-epithelialized corneal grafts. Both Betoptic and Betagan produced minor damage to endothelial microvilli in the intact epithelial group. The de-epithelialized and the grafted-cornea groups had less damage induced by Betoptic than Betagan. Timoptic produced more endothelial damage than Betoptic and Betagan in all groups. Benzalkonium chloride produced minimal endothelial damage. Results indicate that Betoptic produces less endothelial toxicity than the two non-specific beta blockers when corneal epithelium is damaged and after penetrating keratoplasty. | Allen RC, Robin AL, Long D, Novack GD, Lue JC, Kaplan G (1988) A combination of levobunolol and dipivefrin for the treatment of glaucoma. Archives of ophthalmology (Chicago, Ill. : 1960) 106, 904-907 [PubMed:3291837] [show Abstract] This double-masked prospective study compared the ocular hypotensive efficacy and the safety of 0.5% and 1% levobunolol hydrochloride with 0.5% timolol maleate when each was administered topically twice daily in combination with 0.1% dipivefrin hydrochloride. Forty-three patients whose intraocular pressure was previously controlled by concomitant treatment with timolol and dipivefrin were randomly assigned to receive 0.5% or 1% levobunolol and 0.1% dipivefrin, or to continue to receive 0.5% timolol and 0.1% dipivefrin for three months. In the groups receiving levobunolol and dipivefrin concurrently, continued intraocular pressure control was achieved equal to that attained with timolol and dipivefrin before study entry. We concluded that concomitant treatment with levobunolol and dipivefrin is equal in both efficacy and safety to concomitant treatment with timolol and dipivefrin. | Boozman FW, Carriker R, Foerster R, Allen RC, Novack GD, Batoosingh AL (1988) Long-term evaluation of 0.25% levobunolol and timolol for therapy for elevated intraocular pressure. Archives of ophthalmology (Chicago, Ill. : 1960) 106, 614-618 [PubMed:3282501] [show Abstract] In a one-year, double-masked, randomized study, the ocular hypotensive efficacy of twice-daily treatment with 0.25% levobunolol hydrochloride or timolol maleate was evaluated in 78 patients with glaucoma or ocular hypertension (phase 1). If intraocular pressure (IOP) was not well controlled during the study, the concentration of medication was increased to 0.5%, and the patient was followed up for an additional three months (phase 2). During phase 1, the mean IOP was reduced by 4.6 mm Hg in the timolol treatment group and by 5.1 mm Hg in the levobunolol treatment group. Seventy-one percent (29/41) of the patients in the timolol treatment group and 70% (26/37) of the patients in the levobunolol treatment group successfully completed phase 1. Of those patients who required the higher concentration of medication, 89% (8/11) in the timolol treatment group and 75% (3/4) in the levobunolol treatment group successfully completed phase 2. Higher concentration, however, did not produce greater IOP reduction. No statistically or clinically significant differences between the groups were noted in any of the efficacy or safety variables evaluated. | Seamone C, LeBlanc R, Saheb N, Novack G (1988) Efficacy of twice-daily levobunolol in the treatment of elevated intraocular pressure. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie 23, 168-170 [PubMed:3293726] [show Abstract] The efficacy of twice-daily treatment with 0.5% levobunolol hydrochloride was compared with that of 0.5% timolol maleate in 27 patients with open-angle glaucoma or ocular hypertension in a double-blind randomized trial. At all follow-up visits the patients in both groups had significantly decreased intraocular pressure (p less than 0.05); there was no significant difference between the groups. Levobunolol produced significant decreases in mean heart rate (p less than 0.05). One patient with an undisclosed history of childhood asthma experienced bronchospasm related to an acute upper respiratory tract infection while receiving levobunolol. Neither drug caused any significant ocular problems. The results show a clear ocular hypotensive effect with twice-daily 0.5% levobunolol. | Tang-Liu DD, Shackleton M, Richman JB (1988) Ocular metabolism of levobunolol. Journal of ocular pharmacology 4, 269-278 [PubMed:3058836] [show Abstract] Dihydrobunolol is an ocular metabolite equipotent to levobunolol. In order to understand the formation and distribution of dihydrobunolol after an ophthalmic dose of levobunolol, studies in vitro and in vivo were initiated. The metabolism of levobunolol to dihydrobunolol was investigated using an organ-culture technique. The corneal formation of dihydrobunolol was pH-dependent and increased as the pH of the incubation fluid increased from 5.3 to 8.3. Its formation from levobunolol was saturable with Vmax and Km values (pH 7.4) of 13.2 nmol/min/gm of cornea and 1.48 mM, respectively. After a topical dose of 0.5% levobunolol hydrochloride to rabbit eyes, rapid absorption of levobunolol and facila formation of dihydrobunolol were noted. The drug concentration in the eye drop (approximately 17 mM) was much higher than Km and would saturate the epithelial reductase system in the cornea during drug absorption. The total concentrations of levobunolol and dihydrobunolol in ocular tissues were in the micromolar range throughout the experimental period. Dihydrobunolol, after distribution equilibrium, was the major drug-derived species in the cornea, aqueous humor, and iris-ciliary body. The study results indicated pH-dependent and capacity-limited formation of dihydrobunolol in the cornea. Buffering capacity and the drug concentration in the ophthalmic dose are important formulation strategies because they may affect the rate and the extent of dihydrobunolol formation in the epithelial cell layers of the cornea. | Trope GE, Liu GS, Basu PK (1988) Toxic effects of topically administered Betagan, Betoptic, and Timoptic on regenerating corneal epithelium. Journal of ocular pharmacology 4, 359-366 [PubMed:3246571] [show Abstract] Re-epithelialization of 40 iatrogenic cornea ulcers produced in rabbits with iodine vapour burn were studied after topical administration of Betagan, Betoptic or Timoptic. At 24 hours there was no statistical difference in the wound healing rates among all the treated animal groups. At 48 hours, all the drug-treated groups were significantly different from the control group (p less than 0.05). There was no difference between the Betagan and Betoptic treated groups but the Timoptic-treated group was slower (p less than 0.05) than the Betoptic treated group, while the difference between the Timoptic and Betagan treated groups is not significant. At 72 hours the re-epithelialization rate of the Timoptic treated group was significantly slower than both the Betagan and Betoptic treated groups (p less than 0.05). By the 16th day following ulceration SEM examination revealed the Timoptic treated group had extensive epithelial cell desquamation, as well as hole formation and plasma membrane disruption. The Betagan treated corneas had mild superficial epithelial changes with loss of microvilli or slight desquamation. The Betoptic treated corneas were completely healed. In conclusion, Betagan is less toxic than Timoptic. Betoptic is the least toxic of the three drugs to regenerating rabbit corneal epithelium. | Tierney DW (1987) Betaxolol and levobunolol: new beta-blocking antiglaucoma agents. Journal of the American Optometric Association 58, 722-727 [PubMed:2895783] [show Abstract] The Food and Drug Administration has recently approved the use of two new ophthalmic beta-adrenergic antagonistic agents: betaxolol hydrochloride (Betoptic) and levobunolol hydrochloride (Betagan). This paper reviews the history, pharmacologic properties, clinical efficacy and potential side effects of this expanding class of antiglaucoma medication. | Bensinger RE, Keates EU, Gofman JD, Novack GD, Duzman E (1985) Levobunolol. A three-month efficacy study in the treatment of glaucoma and ocular hypertension. Archives of ophthalmology (Chicago, Ill. : 1960) 103, 375-378 [PubMed:3883971] [show Abstract] The ocular hypotensive effect and the safety of levobunolol hydrochloride (0.5% and 1%) were compared with vehicle in this double-masked study of 42 patients with chronic open-angle glaucoma or ocular hypertension. After a washout of ocular hypotensive medication, patients received one of the three test treatments in both eyes twice daily for three months. Both concentrations of levobunolol produced significant reductions in intraocular pressure, while decreases in vehicle-treated patients were minimal. Over the three-month study period, average pressure reductions were approximately 9.0 mm Hg in patients receiving either concentration of levobunolol and 0.5 mm Hg in patients receiving vehicle. Fewer patients were terminated from the study for inadequately controlled intraocular pressure in the levobunolol groups than in the vehicle group. No patients were terminated for drug-related adverse experiences. |
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