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George W Padberg - One of the best experts on this subject based on the ideXlab platform.
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effects of training and Albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy
Journal of Neurology, 2007Co-Authors: E L Van Der Kooi, Eline Lindeman, Jan C M Hendriks, Joke S Kalkman, B G M Van Engelen, Gijs Bleijenberg, George W PadbergAbstract:We recently reported a randomised controlled trial on the efficacy of strength training and the β 2-adrenergic agonist Albuterol in patients with facioscapulohumeral muscular dystrophy (FSHD). Strength training and Albuterol appeared safe interventions with limited positive effect on muscle strength and volume. We concurrently explored the prevalence and the characteristics of pain and fatigue in the participating FSHD patients, because these are probably underreported but clinically relevant symptoms in this disorder. Next, we studied the effects of Albuterol and strength training on pain, experienced fatigue, healthrelated functional status and psychological distress. Sixty-five patients were randomised to strength training of elbow flexors and ankle dorsiflexors or nontraining. After 26 weeks, Albuterol (sustained-release, 8 mg bid) was added in a randomised, doubleblind, placebo-controlled design. Outcomes comprised self-reported pain, experienced fatigue, functional status and psychological distress obtained with validated questionnaires at 52 weeks. Eighty percent of patients reported chronic persistent or periodic, multifocal pains. Thirtyfour percent of the participants were severely fatigued. Strength training and Albuterol failed to have a significant effect on all outcomes. Pain and fatigue are important features in FSHD. Strength training and Albuterol do not have a positive or negative effect on pain, experienced fatigue, functional status and psychological distress.
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effects of training and Albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy
Journal of Neurology, 2007Co-Authors: E L Van Der Kooi, Eline Lindeman, Jan C M Hendriks, Joke S Kalkman, Gijs Bleijenberg, B G M Van Engelen, George W PadbergAbstract:BACKGROUND : We recently reported a randomised controlled trial on the efficacy of strength training and the beta2-adrenergic agonist Albuterol in patients with facioscapulohumeral muscular dystrophy (FSHD). Strength training and Albuterol appeared safe interventions with limited positive effect on muscle strength and volume. We concurrently explored the prevalence and the characteristics of pain and fatigue in the participating FSHD patients, because these are probably underreported but clinically relevant symptoms in this disorder. Next, we studied the effects of Albuterol and strength training on pain, experienced fatigue, health-related functional status and psychological distress. METHODS : Sixty-five patients were randomised to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks, Albuterol (sustained-release, 8 mg bid) was added in a randomised, double-blind, placebo-controlled design. Outcomes comprised self-reported pain, experienced fatigue, functional status and psychological distress obtained with validated questionnaires at 52 weeks. RESULTS : Eighty percent of patients reported chronic persistent or periodic, multifocal pains. Thirty-four percent of the participants were severely fatigued. Strength training and Albuterol failed to have a significant effect on all outcomes. CONCLUSIONS : Pain and fatigue are important features in FSHD. Strength training and Albuterol do not have a positive or negative effect on pain, experienced fatigue, functional status and psychological distress.
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strength training and Albuterol in facioscapulohumeral muscular dystrophy
Neurology, 2004Co-Authors: E L Van Der Kooi, O J M Vogels, R J G P Van Asseldonk, Eline Lindeman, Jan C M Hendriks, M Wohlgemuth, S M Van Der Maarel, George W PadbergAbstract:BACKGROUND: In animals and healthy volunteers beta2-adrenergic agonists increase muscle strength and mass, in particular when combined with strength training. In patients with facioscapulohumeral muscular dystrophy (FSHD) Albuterol may exert anabolic effects. The authors evaluated the effect of strength training and Albuterol on muscle strength and volume in FSHD. METHODS: Sixty-five patients were randomized to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks Albuterol (sustained-release, 8 mg BID) was added in a randomized, double-blind, placebo-controlled design. Primary outcome was maximum voluntary isometric strength (MVIC) at 52 weeks. Secondary outcomes comprised dynamic strength and muscle volume. RESULTS: Training and Albuterol were well tolerated. Training of elbow flexors did not result in a significant effect on MVIC, but dynamic strength improved significantly. Elbow flexor MVIC strength increased significantly in Albuterol vs placebo treated patients. Ankle dorsiflexor strength decreased in all groups. Eleven out of twelve non-trained muscles in the Albuterol group showed a positive effect on MVIC compared to the placebo group (p < 0.05 in seven muscle groups). Muscle volume decreased in the placebo-treated, and increased in the Albuterol-treated patients. No synergistic or antagonistic effects were observed between training and Albuterol. CONCLUSIONS: In FSHD strength training and Albuterol appear safe interventions with limited positive effect on muscle strength and volume. Consequences of prolonged use are presently unclear, which precludes routine prescription.
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strength training and Albuterol in facioscapulohumeral muscular dystrophy
Neurology, 2004Co-Authors: E L Van Der Kooi, O J M Vogels, Eline Lindeman, Jan C M Hendriks, M Wohlgemuth, R J G P Van Asseldonk, S M Van Der Maarel, George W PadbergAbstract:Background: In animals and healthy volunteers β2-adrenergic agonists increase muscle strength and mass, in particular when combined with strength training. In patients with facioscapulohumeral muscular dystrophy (FSHD) Albuterol may exert anabolic effects. The authors evaluated the effect of strength training and Albuterol on muscle strength and volume in FSHD. Methods: Sixty-five patients were randomized to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks Albuterol (sustained-release, 8 mg BID) was added in a randomized, double-blind, placebo-controlled design. Primary outcome was maximum voluntary isometric strength (MVIC) at 52 weeks. Secondary outcomes comprised dynamic strength and muscle volume. Results: Training and Albuterol were well tolerated. Training of elbow flexors did not result in a significant effect on MVIC, but dynamic strength improved significantly. Elbow flexor MVIC strength increased significantly in Albuterol vs placebo treated patients. Ankle dorsiflexor strength decreased in all groups. Eleven out of twelve non-trained muscles in the Albuterol group showed a positive effect on MVIC compared to the placebo group (p Conclusions: In FSHD strength training and Albuterol appear safe interventions with limited positive effect on muscle strength and volume. Consequences of prolonged use are presently unclear, which precludes routine prescription.
S Degraw - One of the best experts on this subject based on the ideXlab platform.
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the safety and efficacy of nebulized levAlbuterol compared with racemic Albuterol and placebo in the treatment of asthma in pediatric patients
The Journal of Allergy and Clinical Immunology, 1999Co-Authors: Sandra M. Gawchik, D S Reasner, Consuelo L. Saccar, Michael Noonan, S DegrawAbstract:Abstract Background: Limited dose-response information is available for nebulized β 2 -agonists, especially in young children. Objective: The purpose of this study was to determine the safety and efficacy of increasing doses of nebulized levAlbuterol (Xopenex; the pure R-isomer of racemic Albuterol) and racemic Albuterol compared with placebo in the treatment of asthma in pediatric patients. Methods: In this randomized, double-blind, crossover study, children (aged 3 to 11 years) with asthma (resting FEV 1 50% to 80% of predicted normal [Polgar's] values) were treated with either levAlbuterol, racemic Albuterol, or placebo. Eligible subjects underwent a screening visit followed by 4 treatment visits. At each treatment visit, serial pulmonary function tests were completed before and after the treatment; plasma was collected to determine enantiomer levels, and safety was evaluated. Results: Five 3- to 5-year-old patients and twenty-eight 6- to 11-year-old patients completed the study, and a total of 87 doses of levAlbuterol were administered. In the 6- to 11-year-old group, all doses of levAlbuterol were significantly greater than placebo in peak change and percent peak change in FEV 1 and area under the FEV 1 versus time curve ( P 1 values over the 8-hour study period were similar for levAlbuterol 0.31 and 0.63 mg and racemic Albuterol 2.5 mg and were greatest after levAlbuterol 1.25 mg. Median plasma levels of R-Albuterol depended on dose and were 0.4, 0.7, 1.2, and 1.0 after levAlbuterol 0.31 mg, 0.63 mg, and 1.25 mg and racemic Albuterol 2.5 mg, respectively. All patients in the 2.5-mg racemic Albuterol arm had measurable plasma levels of S-Albuterol, although S-Albuterol levels were undetectable in most patients in the levAlbuterol arms. In a few patients who received levAlbuterol, S-Albuterol levels were detected, which was likely because of the use of racemic Albuterol as a concomitant medication. All active treatments were well tolerated. β-Mediated changes in heart rate, potassium, and glucose were dose dependent for all active treatment groups. Conclusion: LevAlbuterol caused a significantly greater increase in FEV 1 than placebo, and FEV 1 values were comparable with or better than those observed with racemic Albuterol. β-Mediated side effects were lower for an equipotent dose of levAlbuterol when compared with racemic Albuterol. Treatment with levAlbuterol resulted in plasma levels that were dose dependent and had an approximate correlation with pharmacodynamic parameters. (J Allergy Clin Immunol 1999;103:615-21.)
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the safety and efficacy of nebulized levAlbuterol compared with racemic Albuterol and placebo in the treatment of asthma in pediatric patients
The Journal of Allergy and Clinical Immunology, 1999Co-Authors: Sandra M. Gawchik, D S Reasner, Consuelo L. Saccar, Michael Noonan, S DegrawAbstract:Abstract Background: Limited dose-response information is available for nebulized β 2 -agonists, especially in young children. Objective: The purpose of this study was to determine the safety and efficacy of increasing doses of nebulized levAlbuterol (Xopenex; the pure R-isomer of racemic Albuterol) and racemic Albuterol compared with placebo in the treatment of asthma in pediatric patients. Methods: In this randomized, double-blind, crossover study, children (aged 3 to 11 years) with asthma (resting FEV 1 50% to 80% of predicted normal [Polgar's] values) were treated with either levAlbuterol, racemic Albuterol, or placebo. Eligible subjects underwent a screening visit followed by 4 treatment visits. At each treatment visit, serial pulmonary function tests were completed before and after the treatment; plasma was collected to determine enantiomer levels, and safety was evaluated. Results: Five 3- to 5-year-old patients and twenty-eight 6- to 11-year-old patients completed the study, and a total of 87 doses of levAlbuterol were administered. In the 6- to 11-year-old group, all doses of levAlbuterol were significantly greater than placebo in peak change and percent peak change in FEV 1 and area under the FEV 1 versus time curve ( P 1 values over the 8-hour study period were similar for levAlbuterol 0.31 and 0.63 mg and racemic Albuterol 2.5 mg and were greatest after levAlbuterol 1.25 mg. Median plasma levels of R-Albuterol depended on dose and were 0.4, 0.7, 1.2, and 1.0 after levAlbuterol 0.31 mg, 0.63 mg, and 1.25 mg and racemic Albuterol 2.5 mg, respectively. All patients in the 2.5-mg racemic Albuterol arm had measurable plasma levels of S-Albuterol, although S-Albuterol levels were undetectable in most patients in the levAlbuterol arms. In a few patients who received levAlbuterol, S-Albuterol levels were detected, which was likely because of the use of racemic Albuterol as a concomitant medication. All active treatments were well tolerated. β-Mediated changes in heart rate, potassium, and glucose were dose dependent for all active treatment groups. Conclusion: LevAlbuterol caused a significantly greater increase in FEV 1 than placebo, and FEV 1 values were comparable with or better than those observed with racemic Albuterol. β-Mediated side effects were lower for an equipotent dose of levAlbuterol when compared with racemic Albuterol. Treatment with levAlbuterol resulted in plasma levels that were dose dependent and had an approximate correlation with pharmacodynamic parameters. (J Allergy Clin Immunol 1999;103:615-21.)
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improved bronchodilation with levAlbuterol compared with racemic Albuterol in patients with asthma
The Journal of Allergy and Clinical Immunology, 1998Co-Authors: H S Nelson, G Bensch, W W Pleskow, R Disantostefano, S Degraw, D S Reasner, T E Rollins, P D RubinAbstract:Abstract Background: Racemic Albuterol is an equal mixture of (R)-Albuterol (levAlbuterol), which is responsible for the bronchodilator effect, and (S)-Albuterol, which provides no benefit and may be detrimental. Objective: We sought to compare 2 doses of a single enantiomer, levAlbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levAlbuterol administered as racemic Albuterol with placebo in patients with moderate-to-severe asthma. Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV 1 after 4 weeks. Results: The change in peak FEV 1 response to the first dose in the combined levAlbuterol group was significantly greater compared with the combined racemic Albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV 1 was similar for levAlbuterol 0.63 mg and racemic Albuterol 2.5 mg and greatest for levAlbuterol 1.25 mg. Racemic Albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV 1 was seen after levAlbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and β-adrenergic side effects after administration of levAlbuterol 0.63 mg were reduced relative to levAlbuterol 1.25 mg or racemic Albuterol 2.5 mg. At week 4, the predose FEV 1 value was greatest in patients who received levAlbuterol or placebo when compared with those who received racemic Albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. Conclusion: LevAlbuterol appears to provide a better therapeutic index than the standard dose of racemic Albuterol. These results support the concept that (S)-Albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)
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improved bronchodilation with levAlbuterol compared with racemic Albuterol in patients with asthma
The Journal of Allergy and Clinical Immunology, 1998Co-Authors: H S Nelson, G Bensch, W W Pleskow, R Disantostefano, S Degraw, D S Reasner, T E Rollins, P D RubinAbstract:Abstract Background: Racemic Albuterol is an equal mixture of (R)-Albuterol (levAlbuterol), which is responsible for the bronchodilator effect, and (S)-Albuterol, which provides no benefit and may be detrimental. Objective: We sought to compare 2 doses of a single enantiomer, levAlbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levAlbuterol administered as racemic Albuterol with placebo in patients with moderate-to-severe asthma. Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV 1 after 4 weeks. Results: The change in peak FEV 1 response to the first dose in the combined levAlbuterol group was significantly greater compared with the combined racemic Albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV 1 was similar for levAlbuterol 0.63 mg and racemic Albuterol 2.5 mg and greatest for levAlbuterol 1.25 mg. Racemic Albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV 1 was seen after levAlbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and β-adrenergic side effects after administration of levAlbuterol 0.63 mg were reduced relative to levAlbuterol 1.25 mg or racemic Albuterol 2.5 mg. At week 4, the predose FEV 1 value was greatest in patients who received levAlbuterol or placebo when compared with those who received racemic Albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. Conclusion: LevAlbuterol appears to provide a better therapeutic index than the standard dose of racemic Albuterol. These results support the concept that (S)-Albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)
Leslie Hendeles - One of the best experts on this subject based on the ideXlab platform.
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continuous Albuterol with benzalkonium in children hospitalized with severe asthma
Pediatrics, 2020Co-Authors: Matthew C Pertzborn, Mutasim Abuhasan, Sreekala Prabhakaran, Dawn Baker, Leslie HendelesAbstract:BACKGROUND AND OBJECTIVES: The Albuterol dropper bottle used to prepare solutions for continuous nebulization contains the preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. We hypothesized that BAC would decrease the therapeutic efficacy of Albuterol in patients with acute asthma exacerbations. METHODS: We performed a retrospective cohort study comparing the clinical outcomes of patients RESULTS: A total of 477 patients were included in the analysis (236 exposed to BAC and 241 controls). The duration of continuous nebulization was significantly longer in the BAC group than in the control group (median of 9 vs 6 hours; 15.7% required continuous nebulization compared to 5.8% of controls at 24 hours). The control group was 79% more likely to stop continuous nebulization at any particular point in time (hazard ratio 1.79; 95% confidence interval: 1.45 to 2.22; P CONCLUSIONS: BAC is a functional Albuterol antagonist associated with a longer duration of continuous Albuterol nebulization treatment and additional respiratory support, suggesting that preservative-free Albuterol formulations are safer for use in continuous nebulization.
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benzalkonium chloride a bronchoconstricting preservative in continuous Albuterol nebulizer solutions
Pharmacotherapy, 2017Co-Authors: Sreekala Prabhakaran, Mutasim Abuhasan, Leslie HendelesAbstract:Background For convenience, many pediatric hospitals are preparing solutions for continuous nebulized Albuterol (CNA) using the 0.5% 20 mL multi-dose Albuterol dropper bottle. This product contains benzalkonium chloride (BAC) which, by itself, produces bronchospasm that is dose-dependent and cumulative. The bronchoconstrictive effects of BA are greater in patients with more severe airway obstruction and increased airway responsiveness. Concerns Use of BAC-containing Albuterol during severe acute asthma exacerbations may antagonize the bronchodilator response to Albuterol, prolong treatment, and increase the risk of Albuterol-related systemic adverse effects. Such a deleterious effect of BAC is difficult to detect since some patients improve slowly or may even worsen during treatment. Conclusion We recommend that only preservative-free Albuterol products be used. This article is protected by copyright. All rights reserved.
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benzalkonium chloride a bronchoconstricting preservative in continuous Albuterol nebulizer solutions
Pharmacotherapy, 2017Co-Authors: Sreekala Prabhakaran, Mutasim Abuhasan, Leslie HendelesAbstract:For convenience, many pediatric hospitals are preparing solutions for continuous nebulized Albuterol using the 0.5% 20-ml multidose Albuterol dropper bottle. This product contains benzalkonium chloride (BAC) that, by itself, produces bronchospasm that is dose dependent and cumulative. The bronchoconstrictive effects of BAC are greater in patients with more severe airway obstruction and increased airway responsiveness. Use of BAC-containing Albuterol during severe acute asthma exacerbations may antagonize the bronchodilator response to Albuterol, prolong treatment, and increase the risk of Albuterol-related systemic adverse effects. Such a deleterious effect of BAC is difficult to detect because some patients improve slowly or may even worsen during treatment. We recommend that only preservative-free Albuterol products be used.
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levAlbuterol nebulizer solution is it worth five times the cost of Albuterol
Pharmacotherapy, 2000Co-Authors: Michael J Asmus, Leslie HendelesAbstract:Albuterol is a 50:50 mixture of R-Albuterol, the active enantiomer, and S-Albuterol, which appears to be inactive in humans. The Food and Drug Administration recently approved levAlbuterol, the pure R-isomer, as a preservative-free nebulizer solution. Published studies indicate that it is neither safer nor more effective than an equimolar dose of racemic Albuterol (levAlbuterol 1.25 mg = Albuterol 2.5 mg). However, these studies were conducted in patients with stable asthma (at the top of the dose-response curve), whereas a nebulized bronchodilator most likely would be used by patients with an acute exacerbation. Because such patients, in the hospital setting, often require higher doses of Albuterol, the manufacturer's recommended dose of levAlbuterol is likely to be too low for rescue therapy. LevAlbuterol may cost as much as 5 times more than racemic Albuterol, depending on purchase method. We conclude that levAlbuterol offers no advantage over Albuterol but is likely to be more costly.
W W Pleskow - One of the best experts on this subject based on the ideXlab platform.
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a cumulative dose study of levAlbuterol and racemic Albuterol administered by hydrofluoroalkane 134a metered dose inhaler in asthmatic subjects
The Journal of Allergy and Clinical Immunology, 2008Co-Authors: Kenneth Tripp, Elizabeth B Goodwin, W W Pleskow, Rudolf A Baumgartner, William K Mcvicar, Parameswaran Nair, Jonathan Corren, John P HanrahanAbstract:Background The short-acting β 2 -agonists levAlbuterol and racemic Albuterol are available for administration through a hydrofluoroalkane-134a (HFA) metered-dose inhaler (MDI). Objective This study compared the short-term safety and efficacy of cumulative doses of levAlbuterol HFA MDI and racemic Albuterol HFA MDI in asthmatic subjects. Methods This was a randomized, modified-blind, active-controlled, multicenter, 2-way crossover study. Subjects (n = 49) were randomized to 16 cumulative doses (1×, 2×, 4×, 8×, and 16×) of levAlbuterol (45 μg per dose) or racemic Albuterol (90 μg per dose) administered over a 2-hour period. After a 7-day washout period, subjects were crossed over to the other treatment. After each dose, safety outcomes and pulmonary function were assessed. Results Heart rate and (R)-Albuterol exposure increased for both racemic Albuterol HFA and levAlbuterol HFA. For cumulative doses of 8× or greater, racemic Albuterol HFA treatment had greater increases in mean heart rate than levAlbuterol HFA (least-squares mean [± SD] difference at the 8× dose was 2.8 beats/min [95% CI, 0.3-5.3] and at the 16× dose was 3.5 beats/min [95% CI, 0.6-6.4]). (R)-Albuterol plasma levels ranged from 10% to 18% higher after racemic Albuterol HFA MDI dosing versus after levAlbuterol HFA MDI. FEV 1 improvements were similar for both treatments. The relative potencies of the 2 therapies, based on FEV 1 , were similar (ratio, 1.1 [90% CI, 0.9-1.2]; Finney method). Conclusion In this study single-day cumulative dosing of asthmatic subjects with levAlbuterol HFA MDI or racemic Albuterol HFA MDI resulted in similar improvements in FEV 1 and tolerability. Plasma (R)-Albuterol levels and mean heart rate were less with levAlbuterol HFA MDI.
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pairwise comparison of levAlbuterol versus racemic Albuterol in the treatment of moderate to severe asthma
Allergy and Asthma Proceedings, 2004Co-Authors: W W Pleskow, H S Nelson, Raymond Claus, Kendyl Schaefer, James M RoachAbstract:The object of this study is a post hoc pairwise comparison of levAlbuterol versus racemic Albuterol for asthma in a multicenter, double-blind, randomized, placebo-controlled clinical trial. The participants are patients ≥12 years of age (n = 362) with FEV 1 45-70% of predicted. The patients received nebulized levAlbuterol (0.63 or 1.25 mg), racemic Albuterol (1.25 or 2.5 mg), or placebo t.i.d. for 4 weeks. The primary endpoints, published in Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levAlbuterol compared with racemic Albuterol in patients with asthma. J Allergy Clin Immunol 102:943-952, 1998, included comparisons of active treatments with placebo and of the combined levAlbuterol with the combined racemic Albuterol groups for pulmonary function and rescue medication use. After the first dose, levAlbuterol 1.25 mg produced a significantly greater increase in the mean peak change in FEV 1 compared with both doses of racemic Albuterol (p < 0.03) in all patients and in those with more severe asthma. LevAlbuterol 1.25 mg also produced a significantly greater (p < 0.05) mean area under the curve (AUC) of the FEV 1 versus time plot (AUC FEV 1 ) compared with all other treatments after the first dose in all patients and in the subset with mare severe disease, illustrating better overall improvement in FEV 1 . Active treatment groups demonstrated significant improvements compared with the placebo group (p < 0.05), except for A UC FEV 1 in the racemic Albuterol 1.25-mg group at week 4. LevAlbuterol in the absence of the (S)-isomer provided greater bronchodilation ,than the same quantity of (R)-Albuterol delivered as the racemate. These data suggest that (S)-Albuterol may compromise the efficacy of (R)-Albuterol.
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improved bronchodilation with levAlbuterol compared with racemic Albuterol in patients with asthma
The Journal of Allergy and Clinical Immunology, 1998Co-Authors: H S Nelson, G Bensch, W W Pleskow, R Disantostefano, S Degraw, D S Reasner, T E Rollins, P D RubinAbstract:Abstract Background: Racemic Albuterol is an equal mixture of (R)-Albuterol (levAlbuterol), which is responsible for the bronchodilator effect, and (S)-Albuterol, which provides no benefit and may be detrimental. Objective: We sought to compare 2 doses of a single enantiomer, levAlbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levAlbuterol administered as racemic Albuterol with placebo in patients with moderate-to-severe asthma. Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV 1 after 4 weeks. Results: The change in peak FEV 1 response to the first dose in the combined levAlbuterol group was significantly greater compared with the combined racemic Albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV 1 was similar for levAlbuterol 0.63 mg and racemic Albuterol 2.5 mg and greatest for levAlbuterol 1.25 mg. Racemic Albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV 1 was seen after levAlbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and β-adrenergic side effects after administration of levAlbuterol 0.63 mg were reduced relative to levAlbuterol 1.25 mg or racemic Albuterol 2.5 mg. At week 4, the predose FEV 1 value was greatest in patients who received levAlbuterol or placebo when compared with those who received racemic Albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. Conclusion: LevAlbuterol appears to provide a better therapeutic index than the standard dose of racemic Albuterol. These results support the concept that (S)-Albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)
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improved bronchodilation with levAlbuterol compared with racemic Albuterol in patients with asthma
The Journal of Allergy and Clinical Immunology, 1998Co-Authors: H S Nelson, G Bensch, W W Pleskow, R Disantostefano, S Degraw, D S Reasner, T E Rollins, P D RubinAbstract:Abstract Background: Racemic Albuterol is an equal mixture of (R)-Albuterol (levAlbuterol), which is responsible for the bronchodilator effect, and (S)-Albuterol, which provides no benefit and may be detrimental. Objective: We sought to compare 2 doses of a single enantiomer, levAlbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levAlbuterol administered as racemic Albuterol with placebo in patients with moderate-to-severe asthma. Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV 1 after 4 weeks. Results: The change in peak FEV 1 response to the first dose in the combined levAlbuterol group was significantly greater compared with the combined racemic Albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV 1 was similar for levAlbuterol 0.63 mg and racemic Albuterol 2.5 mg and greatest for levAlbuterol 1.25 mg. Racemic Albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV 1 was seen after levAlbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and β-adrenergic side effects after administration of levAlbuterol 0.63 mg were reduced relative to levAlbuterol 1.25 mg or racemic Albuterol 2.5 mg. At week 4, the predose FEV 1 value was greatest in patients who received levAlbuterol or placebo when compared with those who received racemic Albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. Conclusion: LevAlbuterol appears to provide a better therapeutic index than the standard dose of racemic Albuterol. These results support the concept that (S)-Albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)
H S Nelson - One of the best experts on this subject based on the ideXlab platform.
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pairwise comparison of levAlbuterol versus racemic Albuterol in the treatment of moderate to severe asthma
Allergy and Asthma Proceedings, 2004Co-Authors: W W Pleskow, H S Nelson, Raymond Claus, Kendyl Schaefer, James M RoachAbstract:The object of this study is a post hoc pairwise comparison of levAlbuterol versus racemic Albuterol for asthma in a multicenter, double-blind, randomized, placebo-controlled clinical trial. The participants are patients ≥12 years of age (n = 362) with FEV 1 45-70% of predicted. The patients received nebulized levAlbuterol (0.63 or 1.25 mg), racemic Albuterol (1.25 or 2.5 mg), or placebo t.i.d. for 4 weeks. The primary endpoints, published in Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levAlbuterol compared with racemic Albuterol in patients with asthma. J Allergy Clin Immunol 102:943-952, 1998, included comparisons of active treatments with placebo and of the combined levAlbuterol with the combined racemic Albuterol groups for pulmonary function and rescue medication use. After the first dose, levAlbuterol 1.25 mg produced a significantly greater increase in the mean peak change in FEV 1 compared with both doses of racemic Albuterol (p < 0.03) in all patients and in those with more severe asthma. LevAlbuterol 1.25 mg also produced a significantly greater (p < 0.05) mean area under the curve (AUC) of the FEV 1 versus time plot (AUC FEV 1 ) compared with all other treatments after the first dose in all patients and in the subset with mare severe disease, illustrating better overall improvement in FEV 1 . Active treatment groups demonstrated significant improvements compared with the placebo group (p < 0.05), except for A UC FEV 1 in the racemic Albuterol 1.25-mg group at week 4. LevAlbuterol in the absence of the (S)-isomer provided greater bronchodilation ,than the same quantity of (R)-Albuterol delivered as the racemate. These data suggest that (S)-Albuterol may compromise the efficacy of (R)-Albuterol.
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clinical experience with levAlbuterol
The Journal of Allergy and Clinical Immunology, 1999Co-Authors: H S NelsonAbstract:Abstract Although racemic Albuterol is an effective bronchodilator, regular use has been associated with some loss of bronchodilator potency, decreased protection against bronchoprovocation, increased sensitivity to allergen challenge, and increased sensitivity to some bronchoconstrictor stimuli. In experimental animals racemic Albuterol has produced bronchial hyperresponsiveness, which could also be induced by administration of (S)-Albuterol. These findings suggest that the pure or homochiral formulation of (R)-Albuterol (levAlbuterol) might be more effective as a bronchodilator than the racemic form. Single doses of levAlbuterol provided more prolonged protection against methacholine challenge than the racemate, whereas (S)-Albuterol significantly increased sensitivity to methacholine. In a 4-week study in adults, equivalent amounts of pure levAlbuterol provided greater bronchodilation than did similar amounts of levAlbuterol given as racemic mixtures. Furthermore, after 4 weeks, the baseline morning FEV 1 was lower in those receiving the racemate than in those receiving placebo or levAlbuterol. In a single-dose study in children, the same conclusion regarding greater bronchodilation with pure levAlbuterol compared with the same amount of levAlbuterol in a racemic mixture was confirmed. These studies appear to confirm the greater efficacy of pure levAlbuterol over a similar amount in a racemic mixture. This implies a deleterious effect of (S)-Albuterol on both the acute bronchodilator response and baseline airway caliber, the exact mechanism of which will require further investigation. (J Allergy Clin Immunol 1999;104:S77-84.)
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improved bronchodilation with levAlbuterol compared with racemic Albuterol in patients with asthma
The Journal of Allergy and Clinical Immunology, 1998Co-Authors: H S Nelson, G Bensch, W W Pleskow, R Disantostefano, S Degraw, D S Reasner, T E Rollins, P D RubinAbstract:Abstract Background: Racemic Albuterol is an equal mixture of (R)-Albuterol (levAlbuterol), which is responsible for the bronchodilator effect, and (S)-Albuterol, which provides no benefit and may be detrimental. Objective: We sought to compare 2 doses of a single enantiomer, levAlbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levAlbuterol administered as racemic Albuterol with placebo in patients with moderate-to-severe asthma. Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV 1 after 4 weeks. Results: The change in peak FEV 1 response to the first dose in the combined levAlbuterol group was significantly greater compared with the combined racemic Albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV 1 was similar for levAlbuterol 0.63 mg and racemic Albuterol 2.5 mg and greatest for levAlbuterol 1.25 mg. Racemic Albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV 1 was seen after levAlbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and β-adrenergic side effects after administration of levAlbuterol 0.63 mg were reduced relative to levAlbuterol 1.25 mg or racemic Albuterol 2.5 mg. At week 4, the predose FEV 1 value was greatest in patients who received levAlbuterol or placebo when compared with those who received racemic Albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. Conclusion: LevAlbuterol appears to provide a better therapeutic index than the standard dose of racemic Albuterol. These results support the concept that (S)-Albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)
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improved bronchodilation with levAlbuterol compared with racemic Albuterol in patients with asthma
The Journal of Allergy and Clinical Immunology, 1998Co-Authors: H S Nelson, G Bensch, W W Pleskow, R Disantostefano, S Degraw, D S Reasner, T E Rollins, P D RubinAbstract:Abstract Background: Racemic Albuterol is an equal mixture of (R)-Albuterol (levAlbuterol), which is responsible for the bronchodilator effect, and (S)-Albuterol, which provides no benefit and may be detrimental. Objective: We sought to compare 2 doses of a single enantiomer, levAlbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levAlbuterol administered as racemic Albuterol with placebo in patients with moderate-to-severe asthma. Methods: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV 1 after 4 weeks. Results: The change in peak FEV 1 response to the first dose in the combined levAlbuterol group was significantly greater compared with the combined racemic Albuterol group (0.92 and 0.82 L, respectively; P = .03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV 1 was similar for levAlbuterol 0.63 mg and racemic Albuterol 2.5 mg and greatest for levAlbuterol 1.25 mg. Racemic Albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV 1 was seen after levAlbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and β-adrenergic side effects after administration of levAlbuterol 0.63 mg were reduced relative to levAlbuterol 1.25 mg or racemic Albuterol 2.5 mg. At week 4, the predose FEV 1 value was greatest in patients who received levAlbuterol or placebo when compared with those who received racemic Albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. Conclusion: LevAlbuterol appears to provide a better therapeutic index than the standard dose of racemic Albuterol. These results support the concept that (S)-Albuterol may have detrimental effects on pulmonary function. (J Allergy Clin Immunol 1998;102:943-52.)