Oxitropium Bromide

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Mario Cazzola - One of the best experts on this subject based on the ideXlab platform.

  • Muscarinic Receptor Antagonists.
    Handbook of experimental pharmacology, 2016
    Co-Authors: Maria Gabriella Matera, Mario Cazzola
    Abstract:

    Parasympathetic activity is increased in patients with chronic obstructive pulmonary disease (COPD) and asthma and appears to be the major reversible component of airway obstruction. Therefore, treatment with muscarinic receptor antagonists is an effective bronchodilator therapy in COPD and also in asthmatic patients. In recent years, the accumulating evidence that the cholinergic system controls not only contraction by airway smooth muscle but also the functions of inflammatory cells and airway epithelial cells has suggested that muscarinic receptor antagonists could exert other effects that may be of clinical relevance when we must treat a patient suffering from COPD or asthma. There are currently six muscarinic receptor antagonists licenced for use in the treatment of COPD, the short-acting muscarinic receptor antagonists (SAMAs) ipratropium Bromide and Oxitropium Bromide and the long-acting muscarinic receptor antagonists (LAMAs) aclidinium Bromide, tiotropium Bromide, glycopyrronium Bromide and umeclidinium Bromide. Concerns have been raised about possible associations of muscarinic receptor antagonists with cardiovascular safety, but the most advanced compounds seem to have an improved safety profile. Further beneficial effects of SAMAs and LAMAs are seen when added to existing treatments, including LABAs, inhaled corticosteroids and phosphodiesterase 4 inhibitors. The importance of tiotropium Bromide in the maintenance treatment of COPD, and likely in asthma, has spurred further research to identify new LAMAs. There are a number of molecules that are being identified, but only few have reached the clinical development.

  • bronchodilating effect of Oxitropium Bromide in heart disease patients with exacerbations of copd double blind randomized controlled study
    Respiratory Medicine, 2002
    Co-Authors: Stefano Centanni, Pierachille Santus, F Casanova, Paolo Carlucci, B Boveri, F Castagna, F Di Marco, Mario Cazzola
    Abstract:

    Anti-cholinergic agents are considered the bronchodilator therapy of first-choice in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) associated with heart disease since they may be as effective or more effective than inhaled beta2-agonists and, moreover, they do not interact with cardiac beta-adrenoceptors. The aim of our study was to evaluate the bronchodilator activity of Oxitropium Bromide in outpatients suffering from exacerbations of COPD associated with heart diseases (ischaemic heart disease and/or arrhythmias). We recruited 50 consecutive outpatients (33 males and 17 females, mean age 68.6 years, 15 current smokers and 35 ex-smokers). Each patient performed body plethismography in basal condition and 30 min after inhalation of 200 microg metered dose inhaler (MDI) Oxitropium Bromide administered by a device (Fluspacer). FEV1, FVC, MMEF25-75, sRaw and tRaw were evaluated. Thirty minutes after 200 microg Oxitropium Bromide administration, we observed a significant improvement in FEV1 11.6% +/- 1 (mean +/- SEM) (P<0.01); FVC, MMEF25-75 sRaw variation was respectively: 9.2% +/- 0.6, 31.4 +/- 2.9, -19.9 +/- 1.1. Placebo did not significantly change pulmonary function. Our data suggest that Oxitropium Bromide bronchodilator activity is effective in exacerbations of COPD.

  • Bronchodilating effect of Oxitropium Bromide in heart disease patients with exacerbations of COPD: double-blind, randomized, controlled study.
    Respiratory medicine, 2002
    Co-Authors: Stefano Centanni, Pierachille Santus, F Casanova, Paolo Carlucci, B Boveri, F Castagna, F Di Marco, Mario Cazzola
    Abstract:

    Anti-cholinergic agents are considered the bronchodilator therapy of first-choice in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) associated with heart disease since they may be as effective or more effective than inhaled beta2-agonists and, moreover, they do not interact with cardiac beta-adrenoceptors. The aim of our study was to evaluate the bronchodilator activity of Oxitropium Bromide in outpatients suffering from exacerbations of COPD associated with heart diseases (ischaemic heart disease and/or arrhythmias). We recruited 50 consecutive outpatients (33 males and 17 females, mean age 68.6 years, 15 current smokers and 35 ex-smokers). Each patient performed body plethismography in basal condition and 30 min after inhalation of 200 microg metered dose inhaler (MDI) Oxitropium Bromide administered by a device (Fluspacer). FEV1, FVC, MMEF25-75, sRaw and tRaw were evaluated. Thirty minutes after 200 microg Oxitropium Bromide administration, we observed a significant improvement in FEV1 11.6% +/- 1 (mean +/- SEM) (P

  • Acute effect of pretreatment with single conventional dose of salmeterol on dose-response curve to Oxitropium Bromide in chronic obstructive pulmonary disease
    Thorax, 1999
    Co-Authors: Mario Cazzola, Maria D'amato, C. Califano, F. Di Perna, Stefano Centanni, Claudio F. Donner, Gennaro D'amato
    Abstract:

    BACKGROUND An earlier study documented that, in patients with chronic obstructive pulmonary disease (COPD), addition of ipratropium Bromide at the clinically recommended dose (40 μg) does not produce any further bronchodilation than that achieved with salmeterol 50 μg alone. However, the dose of ipratropium Bromide needed to produce near maximal bronchodilation is several times higher than the customary dosage. The full therapeutic potential of combined salmeterol plus an anticholinergic drug can therefore only be established using doses higher than those currently recommended in the marketing of these agents. A study was undertaken to examine the possible acute effects of higher than conventional doses of an anticholinergic agent on the single dose salmeterol induced bronchodilation in patients with stable and partially reversible COPD. METHODS Thirty two outpatients received 50 μg salmeterol or placebo. Two hours after inhalation a dose-response curve to inhaled Oxitropium Bromide (100 μg/puff) or placebo was constructed using one puff, one puff, two puffs, and two puffs—that is, a total cumulative dose of 600 μg Oxitropium Bromide. Dose increments were given at 20 minute intervals with measurements being made 15 minutes after each dose. On four separate days all patients received one of the following: (1) 50 μg salmeterol + 600 μg Oxitropium Bromide; (2) 50 μg salmeterol + placebo; (3) placebo + 600 μg Oxitropium Bromide; (4) placebo + placebo. RESULTS Salmeterol induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium Bromide elicited an evident dose-dependent increase in forced expiratory volume in one second (FEV 1 ) and this occurred also after pretreatment with salmeterol with a further mean maximum increase of 0.152 l (95% CI of differences 0.124 to 0.180). CONCLUSIONS This study shows that acute pretreatment with 50 μg salmeterol does not block the possibility of inducing more bronchodilation with an anticholinergic agent when a higher than normal dosage of the muscarinic antagonist is used.

  • Incremental benefit of adding Oxitropium Bromide to formoterol in patients with stable COPD.
    Pulmonary pharmacology & therapeutics, 1999
    Co-Authors: Mario Cazzola, C. Califano, F. Di Perna, A. Vinciguerra, M. D»amato
    Abstract:

    The effects of the long-acting β2-agonist formoterol, the anticholinergic drug Oxitropium Bromide, and their combination were compared in 16 patients with partially reversible stable COPD. On each of 4 study days patients inhaled both drugs separated by 180 min in alternate sequence, with formoterol being administered in two doses (formoterol 12 μg + Oxitropium Bromide 200 μg; Oxitropium Bromide 200 μg + formoterol 12 μg; formoterol 24 μg + Oxitropium Bromide 200 μg; Oxitropium Bromide 200 μg + formoterol 24 μg). FEV1and FVC were measured baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. In terms of onset of action, formoterol performed better than Oxitropium Bromide. Within the first 180 min after inhalation formoterol 24 μg was the most effective drug (maximal change in FEV1: formoterol 24 μg = 25.6%, formoterol 12 μg = 21.1%, Oxitropium Bromide = 18.2%). Increased bronchodilation was obtained when the second drug was added, the sequence formoterol 24 μg + Oxitropium Bromide being the most effective (maximal change in FEV1over baseline: formoterol 24 μg + Oxitropium Bromide 28.8%, Oxitropium Bromide + formoterol 24 μg 20.9%, formoterol 12 μg + Oxitropium Bromide 26.6%, Oxitropium Bromide + formoterol 12 μg 22.5%). Significant improvement in pulmonary function may be achieved by giving two different bronchodilators in stable COPD patients. The sequence formoterol 24 μg + Oxitropium Bromide 200 μg seems to be the most effective.

Maria Gabriella Matera - One of the best experts on this subject based on the ideXlab platform.

  • Muscarinic Receptor Antagonists.
    Handbook of experimental pharmacology, 2016
    Co-Authors: Maria Gabriella Matera, Mario Cazzola
    Abstract:

    Parasympathetic activity is increased in patients with chronic obstructive pulmonary disease (COPD) and asthma and appears to be the major reversible component of airway obstruction. Therefore, treatment with muscarinic receptor antagonists is an effective bronchodilator therapy in COPD and also in asthmatic patients. In recent years, the accumulating evidence that the cholinergic system controls not only contraction by airway smooth muscle but also the functions of inflammatory cells and airway epithelial cells has suggested that muscarinic receptor antagonists could exert other effects that may be of clinical relevance when we must treat a patient suffering from COPD or asthma. There are currently six muscarinic receptor antagonists licenced for use in the treatment of COPD, the short-acting muscarinic receptor antagonists (SAMAs) ipratropium Bromide and Oxitropium Bromide and the long-acting muscarinic receptor antagonists (LAMAs) aclidinium Bromide, tiotropium Bromide, glycopyrronium Bromide and umeclidinium Bromide. Concerns have been raised about possible associations of muscarinic receptor antagonists with cardiovascular safety, but the most advanced compounds seem to have an improved safety profile. Further beneficial effects of SAMAs and LAMAs are seen when added to existing treatments, including LABAs, inhaled corticosteroids and phosphodiesterase 4 inhibitors. The importance of tiotropium Bromide in the maintenance treatment of COPD, and likely in asthma, has spurred further research to identify new LAMAs. There are a number of molecules that are being identified, but only few have reached the clinical development.

  • Influence of higher than conventional doses of Oxitropium Bromide on formoterol-induced bronchodilation in COPD.
    Respiratory medicine, 1999
    Co-Authors: Mario Cazzola, Maria Gabriella Matera, Maria D'amato, C. Califano, F. Di Perna, Gennaro Mazzarella
    Abstract:

    Abstract We examined the influence of higher than conventional doses of Oxitropium Bromide on formoterol-induced bronchodilation in patients with partially reversible stable COPD. Twenty outpatients inhaled one or two puffs of formoterol (12 μg puff −1 ), or placebo. Two hours after inhalation, a dose-response curve to inhaled Oxitropium Bromide (100 μg puff −1 ) or placebo was constructed using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 μg Oxitropium Bromide. Doses were given at 20-min intervals and measurements made 15 min after each dose. On six separate days, all patients received one of the following: (1) formoterol 12 μg + Oxitropium Bromide 600 μg, (2) formoterol 12 μg + placebo, (3) formoterol 24 μg + Oxitropium Bromide 600 μg, (4) formoterol 24 μg + placebo, (5) placebo + Oxitropium Bromide 600 μg, or (6) placebo + placebo. Both formoterol 12 μg and 24 μg induced a good bronchodilation (formoterol 12 μg, 0·19–0·20 1; formoterol 24 μg 0·22–0·24 1). The dose-response curve of Oxitropium, but not placebo, showed an evident increase in FEV 1 , with a further significant increase of respectively 0·087 1 and 0·082 1 after the formoterol 12 μg and formoterol 24 μg pre-treatment. This study shows that improved pulmonary function in patients with stable COPD may be achieved by adding Oxitropium 400–600 μg to formoterol. There is not much difference in bronchodilation between combining Oxitropium with formoterol 12 μg or 24 μg. In any case, formoterol 24 μg alone seems sufficient to achieve the same bronchodilation induced by Oxitropium 600 μg alone in most patients.

  • Effects of formoterol, salmeterol or Oxitropium Bromide on airway responses to salbutamol in COPD
    The European respiratory journal, 1998
    Co-Authors: Mario Cazzola, F. Di Perna, A. Vinciguerra, Paolo Noschese, F. Calderaro, Giuseppe Girbino, Maria Gabriella Matera
    Abstract:

    We examined whether a pretreatment with formoterol, Oxitropium Bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 microg formoterol, 50 microg salmeterol, 200 microg Oxitropium Bromide, or placebo on four non-consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100, 100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or Oxitropium Bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; Oxitropium Bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; Oxitropium Bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or Oxitropium Bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or Oxitropium Bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.

  • A comparison of bronchodilating effects of salmeterol and Oxitropium Bromide in stable chronic obstructive pulmonary disease
    Respiratory medicine, 1998
    Co-Authors: Mario Cazzola, Maria Gabriella Matera, C. Califano, F. Di Perna, F. Calderaro, A. Vinciguerra
    Abstract:

    Abstract Anti-cholinergic agents are generally regarded as the bronchodilator therapy of first choice in the treatment of stable chronic obstructive pulmonary disease (COPD), considering that they may be more effective than in inhaled β2-agonist. However, results of the authors' recent studies conflict to some extent with this suggestion because they demonstrate that this is true only for short acting β2-agonists but not for long-acting β2-agonists. Oxitropium Bromide is an anti-cholinergic drug that has been shown to produce a similar degree of bronchodilation to that obtained with ipratropium Bromide, but with a longer-lasting effect. In the present study, the time course of inhaled Oxitropium Bromide bronchodilation in comparison to that of inhaled salmeterol in a group of patients with partially reversible COPD was evaluated. Twelve male patients with moderate to severe COPD participated in the study. The study had a single-bind, cross-over, randomized design. The bronchodilator activity of 50 μg salmeterol hydroxynaphthoate, 200 and 400 μg Oxitropium Bromide and placebo, which were all inhaled from a metered-dose inhaler, was investigated on several non-consecutive days. The highest FVC and FEV1, obtained from one or the other of the reproducible curves, were kept for analysis. Measurements were performed at the following times: immediately before inhalation of treatment, and at 15, 30, 60, 120, 180, 240, 300, 360, 480, 600 and 720 min after inhalation of the individual treatment. Salmeterol tended to have a delayed time to peak effect, but had a longer duration of effect than Oxitropium. The response to salmeterol exceeded the response to 200 μg Oxitropium for 12 h, but its responses were significantly (P

Takateru Izumi - One of the best experts on this subject based on the ideXlab platform.

  • The effects of Oxitropium Bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. A comparison of three different exercise tests.
    American journal of respiratory and critical care medicine, 2000
    Co-Authors: Toru Oga, Koichi Nishimura, Akihiko Ikeda, Mitsuhiro Tsukino, Takashi Hajiro, Takateru Izumi
    Abstract:

    The purpose of the present study was to compare the characteristics of three different exercise tests in evaluating the effects of Oxitropium Bromide on exercise performance. Thirty-eight males with stable chronic obstructive pulmonary disease (COPD) (FEV 1 5 40.8 6 16.5% predicted; mean 6 SD) completed randomized, double-blind, placebo-controlled, crossover studies for each exercise test. The exercise tests were performed 60 min after the inhalation of either Oxitropium Bromide 400 m g or placebo. The patients performed 6-min walking tests (6MWT) on Days 1 and 2, progressive cycle ergometry (PCE) on Days 3 and 4, and cycle endurance tests at 80% of the maximal workload of PCE on Days 5 and 6. Spirometry was conducted before and at 45 and 90 min after the inhalation. Oxitropium Bromide significantly increased FEV 1 as compared with placebo. Oxitropium Bromide increased the endurance time significantly, by 19% (p , 0.001), and caused a small but significant increase in the 6-min walking distance by 1% (p , 0.05), but induced no significant increase in maximal oxygen consumption ( O 2 max) in PCE. The responses in these three exercise tests were different, and we conclude that the endurance test was the most sensitive in detecting the effects of inhaled anticholinergic agents on exercise performance in patients with stable COPD. An endurance procedure may be performed to detect clinical changes in evaluating the effects of Oxitropium Bromide on exercise performance. Patients with chronic obstructive pulmonary disease (COPD) complain of exertional breathlessness and exercise intolerance, mainly due to reduced ventilatory capacity and impaired gas exchange. Inhaled anticholinergic agents are recommended as the first-line drugs to relieve these patients’ symptoms and to improve their airflow limitation (1, 2). Although the bronchodilating effects of these drugs in COPD have been established (3, 4), there is sometimes controversy about whether anticholinergic agents affect exercise performance (5‐10). The effects of anticholinergic bronchodilators may depend on the type of exercise test performed. In investigating the effects of bronchodilators on exercise performance in patients with COPD, a walking test and progressive cycle ergometry (PCE) are often used (5‐10). However, in assessing the effects of pulmonary rehabilitation, endurance tests are sometimes used because measures of endurance may be responsive to training. An effective pulmonary rehabilitation program usually results in an improvement in exercise endurance, but little or no change in maximal exercise capacity (11). Recently, O’Donnell and coworkers reported that after bronchodilator therapy, exercise time was a reliable measure of exercise enV ·

  • Additive effect of Oxitropium Bromide in combination with inhaled corticosteroids in the treatment of elderly patients with chronic asthma
    Allergology International, 1999
    Co-Authors: Koichi Nishimura, Hiroshi Koyama, Kyosuke Ishihara, Tsuyoshi Hasegawa, Satoru Katayama, Akio Nakashima, Takateru Izumi
    Abstract:

    The efficacy of the addition of inhaled Oxitropium Bromide in combination with inhaled corticosteroids in the treatment of elderly asthmatic patients whose asthma is not well controlled was evaluated. A randomized, open-label cross-over trial comparing 4-week treatment periods with and without regular inhalation of 200 μg of Oxitropium Bromide four times per day was performed. Twenty-four patients (mean age ± SD: 62 ± 7 years) completed the study. The dose of beclomethasone dipropionate in this patient group was 1300 ± 800 μg/day. Forced expiratory volume in 1 second (FEV1) was significantly improved after treatment with regular inhalation of Oxitropium Bromide when compared with FEV1 after treatment without Oxitropium (1.73 ± 0.60 vs 1.63 ± 0.68). Both morning and evening peak expiratory flow rates were significantly greater during the treatment period with regular inhalation of Oxitropium Bromide. The score for dyspnea/chest tightness was also significantly improved during the Oxitropium Bromide period. There was no statistically significant improvement in forced vital capacity, scores for other symptoms or the frequency of rescue inhalation of fenoterol. The results of this study demonstrated that the addition of regular inhalation of Oxitropium Bromide is beneficial in elderly asthmatics whose asthma is not well controlled, even when treated with high-dose inhaled steroids.

  • comparative dose response study of three anticholinergic agents and fenoterol using a metered dose inhaler in patients with chronic obstructive pulmonary disease
    Thorax, 1995
    Co-Authors: Akihiko Ikeda, Hiroshi Koyama, Koichi Nishimura, Takateru Izumi
    Abstract:

    BACKGROUND--Inhaled anticholinergics and beta agonists are widely used in the treatment of patients with chronic obstructive pulmonary disease (COPD). However, dosage requirements have not been thoroughly evaluated and comparative dose-response data for these agents are limited. METHODS--Twenty men with stable COPD of mean (SD) age 69.4 (5.8) years and FEV1 0.93 (0.38) litres were studied in randomised, double blind, crossover, placebo controlled experiments. All of the patients received two, four, eight, and 16 puffs of ipratropium Bromide (20 micrograms/puff), flutropium Bromide (30 micrograms/puff), Oxitropium Bromide (100 micrograms/puff), fenoterol (200 micrograms/puff), or placebo in random order on five separate days. Doses were administered by a metered dose inhaler at intervals of 60 minutes to give cumulative doses of two, six, 14, and 30 puffs. Five mg of nebulised salbutamol was administered 60 minutes after the patient had received the final 16 puffs of each regimen. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), heart rate, and blood pressure were measured five minutes before each treatment and 30 minutes after treatment with nebulised salbutamol. RESULTS--FEV1 and FVC reached a plateau after administration of a cumulative dose of 14 puffs of ipratropium Bromide (280 micrograms) or flutropium Bromide (420 micrograms), and after six puffs of Oxitropium Bromide (600 micrograms). There were no differences with respect to maximum increases in FEV1 and FVC amongst the three anticholinergic agents. However, after six puffs Oxitropium Bromide produced a greater increase in FEV1 than either ipratropium Bromide or flutropium Bromide. Fenoterol caused a greater increase in both FEV1 and FVC than the three anticholinergic agents after six puffs, as well as a greater increase in pulse rate. Oxitropium Bromide produced a greater increase in pulse rate than the other anticholinergics after 14 puffs. The incidence of side effects was dose-related and notable adverse effects were reported after 30 puffs of ipratropium Bromide, 14 puffs of Oxitropium Bromide, and two puffs of fenoterol. CONCLUSIONS--Oxitropium Bromide produced a greater bronchodilator effect than either ipratropium Bromide or flutropium Bromide when used at doses of less than six puffs, without apparent side effects. There were, however, no differences in maximal response between these drugs. Fenoterol may have a greater peak bronchodilator effect than the anticholinergic agents but it causes more adverse effects, even at lower doses. Depending upon the balance between efficacy and side effects, Oxitropium Bromide may be preferred in the treatment of patients with COPD.

  • Oxitropium Bromide Improves Exercise Performance in Patients With COPD
    Chest, 1994
    Co-Authors: Akihiko Ikeda, Hiroshi Koyama, Koichi Nishimura, Naoharu Sugiura, Takateru Izumi
    Abstract:

    Inhaled anticholinergics may be the first-line therapy for stable COPD. However, the effect of inhaled anticholinergic agents on exercise capacity is still controversial. Fourteen patients with stable COPD (age, 64.6 ± 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial. All the patients were studied by symptom-limited progressive cycle ergometry before and 90 min after the inhalation of either Oxitropium Bromide, 800 μ g, or an identical placebo. Spirometry was assessed before and after each exercise test. While FEV 1 averaged 0.85 ± 0.34 L at 90 min after the inhalation of placebo, FEV 1 was 1.01 ± 0.41 L at 90 min after the inhalation of Oxitropium, 800 μ g (significant from placebo, p 1 before and after inhalation (r=0.625, p μ g, can improve the exercise capacity of patients with stable COPD. It is suggested that the effect is due to the bronchodilation induced by this drug.

  • a comparison of the bronchodilating effects of Oxitropium Bromide and fenoterol in patients with chronic obstructive pulmonary disease
    Chest, 1993
    Co-Authors: Hiroshi Koyama, Koichi Nishimura, Akihiko Ikeda, Takateru Izumi
    Abstract:

    Oxitropium Bromide is a novel anticholinergic bronchodilator agent. The purpose of this study was to compare the bronchodilating and cardiovascular effects of Oxitropium (0.2 mg), fenoterol (0.4 mg), combined Oxitropium and fenoterol (0.2 mg and 0.4 mg, respectively) over a 10-h test period. Fourteen patients with chronic obstructive pulmonary disease (COPD) (FEV 1 , 0.95±0.38L) were studied in a randomized, double-blind, placebo-controlled trial. Combined Oxitropium and fenoterol produced significantly greater improvements in FEV 1 over a time span of 15 min to 10 h and in the area under the time-FEV 1 curve (AUC) than either Oxitropium or fenoterol alone. The effects of Oxitropium on both FEV, and AUC values were similar to those of fenoterol. Oxitropium resulted in a greater increase in FEV, than the placebo even after 10 h. In contrast, fenoterol produced a significant improvement in the FEV, for only 15 min to 4 h. Oxitropium showed no adverse cardiovascular effects, whereas fenoterol was associated with an increased heart rate at 15 min and 1 h after the administration. We conclude that Oxitropium Bromide is an effective and safe bronchodilator for even elderly patients with COPD.

F. Di Perna - One of the best experts on this subject based on the ideXlab platform.

  • Acute effect of pretreatment with single conventional dose of salmeterol on dose-response curve to Oxitropium Bromide in chronic obstructive pulmonary disease
    Thorax, 1999
    Co-Authors: Mario Cazzola, Maria D'amato, C. Califano, F. Di Perna, Stefano Centanni, Claudio F. Donner, Gennaro D'amato
    Abstract:

    BACKGROUND An earlier study documented that, in patients with chronic obstructive pulmonary disease (COPD), addition of ipratropium Bromide at the clinically recommended dose (40 μg) does not produce any further bronchodilation than that achieved with salmeterol 50 μg alone. However, the dose of ipratropium Bromide needed to produce near maximal bronchodilation is several times higher than the customary dosage. The full therapeutic potential of combined salmeterol plus an anticholinergic drug can therefore only be established using doses higher than those currently recommended in the marketing of these agents. A study was undertaken to examine the possible acute effects of higher than conventional doses of an anticholinergic agent on the single dose salmeterol induced bronchodilation in patients with stable and partially reversible COPD. METHODS Thirty two outpatients received 50 μg salmeterol or placebo. Two hours after inhalation a dose-response curve to inhaled Oxitropium Bromide (100 μg/puff) or placebo was constructed using one puff, one puff, two puffs, and two puffs—that is, a total cumulative dose of 600 μg Oxitropium Bromide. Dose increments were given at 20 minute intervals with measurements being made 15 minutes after each dose. On four separate days all patients received one of the following: (1) 50 μg salmeterol + 600 μg Oxitropium Bromide; (2) 50 μg salmeterol + placebo; (3) placebo + 600 μg Oxitropium Bromide; (4) placebo + placebo. RESULTS Salmeterol induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium Bromide elicited an evident dose-dependent increase in forced expiratory volume in one second (FEV 1 ) and this occurred also after pretreatment with salmeterol with a further mean maximum increase of 0.152 l (95% CI of differences 0.124 to 0.180). CONCLUSIONS This study shows that acute pretreatment with 50 μg salmeterol does not block the possibility of inducing more bronchodilation with an anticholinergic agent when a higher than normal dosage of the muscarinic antagonist is used.

  • Incremental benefit of adding Oxitropium Bromide to formoterol in patients with stable COPD.
    Pulmonary pharmacology & therapeutics, 1999
    Co-Authors: Mario Cazzola, C. Califano, F. Di Perna, A. Vinciguerra, M. D»amato
    Abstract:

    The effects of the long-acting β2-agonist formoterol, the anticholinergic drug Oxitropium Bromide, and their combination were compared in 16 patients with partially reversible stable COPD. On each of 4 study days patients inhaled both drugs separated by 180 min in alternate sequence, with formoterol being administered in two doses (formoterol 12 μg + Oxitropium Bromide 200 μg; Oxitropium Bromide 200 μg + formoterol 12 μg; formoterol 24 μg + Oxitropium Bromide 200 μg; Oxitropium Bromide 200 μg + formoterol 24 μg). FEV1and FVC were measured baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. In terms of onset of action, formoterol performed better than Oxitropium Bromide. Within the first 180 min after inhalation formoterol 24 μg was the most effective drug (maximal change in FEV1: formoterol 24 μg = 25.6%, formoterol 12 μg = 21.1%, Oxitropium Bromide = 18.2%). Increased bronchodilation was obtained when the second drug was added, the sequence formoterol 24 μg + Oxitropium Bromide being the most effective (maximal change in FEV1over baseline: formoterol 24 μg + Oxitropium Bromide 28.8%, Oxitropium Bromide + formoterol 24 μg 20.9%, formoterol 12 μg + Oxitropium Bromide 26.6%, Oxitropium Bromide + formoterol 12 μg 22.5%). Significant improvement in pulmonary function may be achieved by giving two different bronchodilators in stable COPD patients. The sequence formoterol 24 μg + Oxitropium Bromide 200 μg seems to be the most effective.

  • Influence of higher than conventional doses of Oxitropium Bromide on formoterol-induced bronchodilation in COPD.
    Respiratory medicine, 1999
    Co-Authors: Mario Cazzola, Maria Gabriella Matera, Maria D'amato, C. Califano, F. Di Perna, Gennaro Mazzarella
    Abstract:

    Abstract We examined the influence of higher than conventional doses of Oxitropium Bromide on formoterol-induced bronchodilation in patients with partially reversible stable COPD. Twenty outpatients inhaled one or two puffs of formoterol (12 μg puff −1 ), or placebo. Two hours after inhalation, a dose-response curve to inhaled Oxitropium Bromide (100 μg puff −1 ) or placebo was constructed using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 μg Oxitropium Bromide. Doses were given at 20-min intervals and measurements made 15 min after each dose. On six separate days, all patients received one of the following: (1) formoterol 12 μg + Oxitropium Bromide 600 μg, (2) formoterol 12 μg + placebo, (3) formoterol 24 μg + Oxitropium Bromide 600 μg, (4) formoterol 24 μg + placebo, (5) placebo + Oxitropium Bromide 600 μg, or (6) placebo + placebo. Both formoterol 12 μg and 24 μg induced a good bronchodilation (formoterol 12 μg, 0·19–0·20 1; formoterol 24 μg 0·22–0·24 1). The dose-response curve of Oxitropium, but not placebo, showed an evident increase in FEV 1 , with a further significant increase of respectively 0·087 1 and 0·082 1 after the formoterol 12 μg and formoterol 24 μg pre-treatment. This study shows that improved pulmonary function in patients with stable COPD may be achieved by adding Oxitropium 400–600 μg to formoterol. There is not much difference in bronchodilation between combining Oxitropium with formoterol 12 μg or 24 μg. In any case, formoterol 24 μg alone seems sufficient to achieve the same bronchodilation induced by Oxitropium 600 μg alone in most patients.

  • Effects of formoterol, salmeterol or Oxitropium Bromide on airway responses to salbutamol in COPD
    The European respiratory journal, 1998
    Co-Authors: Mario Cazzola, F. Di Perna, A. Vinciguerra, Paolo Noschese, F. Calderaro, Giuseppe Girbino, Maria Gabriella Matera
    Abstract:

    We examined whether a pretreatment with formoterol, Oxitropium Bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 microg formoterol, 50 microg salmeterol, 200 microg Oxitropium Bromide, or placebo on four non-consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100, 100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or Oxitropium Bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; Oxitropium Bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; Oxitropium Bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or Oxitropium Bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or Oxitropium Bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.

  • A comparison of bronchodilating effects of salmeterol and Oxitropium Bromide in stable chronic obstructive pulmonary disease
    Respiratory medicine, 1998
    Co-Authors: Mario Cazzola, Maria Gabriella Matera, C. Califano, F. Di Perna, F. Calderaro, A. Vinciguerra
    Abstract:

    Abstract Anti-cholinergic agents are generally regarded as the bronchodilator therapy of first choice in the treatment of stable chronic obstructive pulmonary disease (COPD), considering that they may be more effective than in inhaled β2-agonist. However, results of the authors' recent studies conflict to some extent with this suggestion because they demonstrate that this is true only for short acting β2-agonists but not for long-acting β2-agonists. Oxitropium Bromide is an anti-cholinergic drug that has been shown to produce a similar degree of bronchodilation to that obtained with ipratropium Bromide, but with a longer-lasting effect. In the present study, the time course of inhaled Oxitropium Bromide bronchodilation in comparison to that of inhaled salmeterol in a group of patients with partially reversible COPD was evaluated. Twelve male patients with moderate to severe COPD participated in the study. The study had a single-bind, cross-over, randomized design. The bronchodilator activity of 50 μg salmeterol hydroxynaphthoate, 200 and 400 μg Oxitropium Bromide and placebo, which were all inhaled from a metered-dose inhaler, was investigated on several non-consecutive days. The highest FVC and FEV1, obtained from one or the other of the reproducible curves, were kept for analysis. Measurements were performed at the following times: immediately before inhalation of treatment, and at 15, 30, 60, 120, 180, 240, 300, 360, 480, 600 and 720 min after inhalation of the individual treatment. Salmeterol tended to have a delayed time to peak effect, but had a longer duration of effect than Oxitropium. The response to salmeterol exceeded the response to 200 μg Oxitropium for 12 h, but its responses were significantly (P

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  • Acute effect of pretreatment with single conventional dose of salmeterol on dose-response curve to Oxitropium Bromide in chronic obstructive pulmonary disease
    Thorax, 1999
    Co-Authors: Mario Cazzola, Maria D'amato, C. Califano, F. Di Perna, Stefano Centanni, Claudio F. Donner, Gennaro D'amato
    Abstract:

    BACKGROUND An earlier study documented that, in patients with chronic obstructive pulmonary disease (COPD), addition of ipratropium Bromide at the clinically recommended dose (40 μg) does not produce any further bronchodilation than that achieved with salmeterol 50 μg alone. However, the dose of ipratropium Bromide needed to produce near maximal bronchodilation is several times higher than the customary dosage. The full therapeutic potential of combined salmeterol plus an anticholinergic drug can therefore only be established using doses higher than those currently recommended in the marketing of these agents. A study was undertaken to examine the possible acute effects of higher than conventional doses of an anticholinergic agent on the single dose salmeterol induced bronchodilation in patients with stable and partially reversible COPD. METHODS Thirty two outpatients received 50 μg salmeterol or placebo. Two hours after inhalation a dose-response curve to inhaled Oxitropium Bromide (100 μg/puff) or placebo was constructed using one puff, one puff, two puffs, and two puffs—that is, a total cumulative dose of 600 μg Oxitropium Bromide. Dose increments were given at 20 minute intervals with measurements being made 15 minutes after each dose. On four separate days all patients received one of the following: (1) 50 μg salmeterol + 600 μg Oxitropium Bromide; (2) 50 μg salmeterol + placebo; (3) placebo + 600 μg Oxitropium Bromide; (4) placebo + placebo. RESULTS Salmeterol induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium Bromide elicited an evident dose-dependent increase in forced expiratory volume in one second (FEV 1 ) and this occurred also after pretreatment with salmeterol with a further mean maximum increase of 0.152 l (95% CI of differences 0.124 to 0.180). CONCLUSIONS This study shows that acute pretreatment with 50 μg salmeterol does not block the possibility of inducing more bronchodilation with an anticholinergic agent when a higher than normal dosage of the muscarinic antagonist is used.

  • Incremental benefit of adding Oxitropium Bromide to formoterol in patients with stable COPD.
    Pulmonary pharmacology & therapeutics, 1999
    Co-Authors: Mario Cazzola, C. Califano, F. Di Perna, A. Vinciguerra, M. D»amato
    Abstract:

    The effects of the long-acting β2-agonist formoterol, the anticholinergic drug Oxitropium Bromide, and their combination were compared in 16 patients with partially reversible stable COPD. On each of 4 study days patients inhaled both drugs separated by 180 min in alternate sequence, with formoterol being administered in two doses (formoterol 12 μg + Oxitropium Bromide 200 μg; Oxitropium Bromide 200 μg + formoterol 12 μg; formoterol 24 μg + Oxitropium Bromide 200 μg; Oxitropium Bromide 200 μg + formoterol 24 μg). FEV1and FVC were measured baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. In terms of onset of action, formoterol performed better than Oxitropium Bromide. Within the first 180 min after inhalation formoterol 24 μg was the most effective drug (maximal change in FEV1: formoterol 24 μg = 25.6%, formoterol 12 μg = 21.1%, Oxitropium Bromide = 18.2%). Increased bronchodilation was obtained when the second drug was added, the sequence formoterol 24 μg + Oxitropium Bromide being the most effective (maximal change in FEV1over baseline: formoterol 24 μg + Oxitropium Bromide 28.8%, Oxitropium Bromide + formoterol 24 μg 20.9%, formoterol 12 μg + Oxitropium Bromide 26.6%, Oxitropium Bromide + formoterol 12 μg 22.5%). Significant improvement in pulmonary function may be achieved by giving two different bronchodilators in stable COPD patients. The sequence formoterol 24 μg + Oxitropium Bromide 200 μg seems to be the most effective.

  • Influence of higher than conventional doses of Oxitropium Bromide on formoterol-induced bronchodilation in COPD.
    Respiratory medicine, 1999
    Co-Authors: Mario Cazzola, Maria Gabriella Matera, Maria D'amato, C. Califano, F. Di Perna, Gennaro Mazzarella
    Abstract:

    Abstract We examined the influence of higher than conventional doses of Oxitropium Bromide on formoterol-induced bronchodilation in patients with partially reversible stable COPD. Twenty outpatients inhaled one or two puffs of formoterol (12 μg puff −1 ), or placebo. Two hours after inhalation, a dose-response curve to inhaled Oxitropium Bromide (100 μg puff −1 ) or placebo was constructed using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 μg Oxitropium Bromide. Doses were given at 20-min intervals and measurements made 15 min after each dose. On six separate days, all patients received one of the following: (1) formoterol 12 μg + Oxitropium Bromide 600 μg, (2) formoterol 12 μg + placebo, (3) formoterol 24 μg + Oxitropium Bromide 600 μg, (4) formoterol 24 μg + placebo, (5) placebo + Oxitropium Bromide 600 μg, or (6) placebo + placebo. Both formoterol 12 μg and 24 μg induced a good bronchodilation (formoterol 12 μg, 0·19–0·20 1; formoterol 24 μg 0·22–0·24 1). The dose-response curve of Oxitropium, but not placebo, showed an evident increase in FEV 1 , with a further significant increase of respectively 0·087 1 and 0·082 1 after the formoterol 12 μg and formoterol 24 μg pre-treatment. This study shows that improved pulmonary function in patients with stable COPD may be achieved by adding Oxitropium 400–600 μg to formoterol. There is not much difference in bronchodilation between combining Oxitropium with formoterol 12 μg or 24 μg. In any case, formoterol 24 μg alone seems sufficient to achieve the same bronchodilation induced by Oxitropium 600 μg alone in most patients.

  • A comparison of bronchodilating effects of salmeterol and Oxitropium Bromide in stable chronic obstructive pulmonary disease
    Respiratory medicine, 1998
    Co-Authors: Mario Cazzola, Maria Gabriella Matera, C. Califano, F. Di Perna, F. Calderaro, A. Vinciguerra
    Abstract:

    Abstract Anti-cholinergic agents are generally regarded as the bronchodilator therapy of first choice in the treatment of stable chronic obstructive pulmonary disease (COPD), considering that they may be more effective than in inhaled β2-agonist. However, results of the authors' recent studies conflict to some extent with this suggestion because they demonstrate that this is true only for short acting β2-agonists but not for long-acting β2-agonists. Oxitropium Bromide is an anti-cholinergic drug that has been shown to produce a similar degree of bronchodilation to that obtained with ipratropium Bromide, but with a longer-lasting effect. In the present study, the time course of inhaled Oxitropium Bromide bronchodilation in comparison to that of inhaled salmeterol in a group of patients with partially reversible COPD was evaluated. Twelve male patients with moderate to severe COPD participated in the study. The study had a single-bind, cross-over, randomized design. The bronchodilator activity of 50 μg salmeterol hydroxynaphthoate, 200 and 400 μg Oxitropium Bromide and placebo, which were all inhaled from a metered-dose inhaler, was investigated on several non-consecutive days. The highest FVC and FEV1, obtained from one or the other of the reproducible curves, were kept for analysis. Measurements were performed at the following times: immediately before inhalation of treatment, and at 15, 30, 60, 120, 180, 240, 300, 360, 480, 600 and 720 min after inhalation of the individual treatment. Salmeterol tended to have a delayed time to peak effect, but had a longer duration of effect than Oxitropium. The response to salmeterol exceeded the response to 200 μg Oxitropium for 12 h, but its responses were significantly (P

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