Effect of Salmeterol and Formoterol in Patients with Chronic Obstructive Pulmonary Disease

doi:10.1006/pulp.1994.1012

Pulmonary Pharmacology

Volume 7, Issue 2, April 1994, Pages 103-107

https://doi.org/10.1006/pulp.1994.1012 Get rights and content

Abstract

Summary: In the present trial we investigated the time course of inhaled salmeterol and formoterol bronchodilation in comparison with that of inhaled salbutamol and placebo in 16 patients with moderate to severe chronic obstructive pulmonary disease (COPD).

The study was performed using a single-blind crossover randomized study. The bronchodilator activity of 200 μg salbutamol, 50 μg salmeterol, 24 μg formoterol and placebo, which were all inhaled from a metered dose inhaler, was investigated.

Our results showed that salmeterol and formoterol are efficacious in reducing airflow obstruction in patients suffering from COPD. We found similar times of onset to improve FEV₁ by 15% for salmeterol and formoterol (salbutamol behaving faster), while the duration of action showed the expected differences between the two long-acting drugs and salbutamol.

The results indicate that long-acting β₂-agonists appear to be very effective in improving airway limitation in patients suffering from COPD. Although the onset of bronchodilation after inhaling salmeterol and formoterol is slightly delayed compared with salbutamol, this is of little clinical importance since in these patients salmeterol and formoterol must be intended for maintenance treatment and not immediate symptomatic relief.

References (0)

Cited by (91)

The use of long acting β<inf>2</inf>-agonists, alone or in combination with inhaled corticosteroids, in Chronic Obstructive Pulmonary Disease (COPD): A risk-benefit analysis
2011, Pharmacology and Therapeutics
Chronic Obstructive Pulmonary Disease (COPD) is a slowly progressive, largely non-reversible pulmonary disease which is characterised by airflow limitation. It is one of the few diseases with an increasing mortality rate and by 2020 it is predicted to be the third leading cause of death. The mainstays of current treatment are long acting β₂ agonists (LABAs) coupled with an increasing reliance on inhaled corticosteroids (ICS). Two LABAs (salmeterol and formoterol) are currently licenced for COPD both as monotherapy and in combination with ICS (fluticasone propionate (FP) and budesonide respectively). A comprehensive review of the risk–benefit of these medicines in COPD is provided here which concludes that there is limited efficacy for LABAs in COPD either alone or in combination with ICS and no overall modification of the disease process. However, where directly compared, combination therapy usually provides an advantage over monotherapy. Importantly the apparent effectiveness of treatment may significantly depend upon the outcome measure chosen with some measures possibly underestimating the extent of benefit. ICS benefit may also be greater in those patients who respond to treatment. Set against this benefit are recent concerns that a number of issues related to the clinical trial design such as prior use of ICS and different withdrawal rates between groups may be significantly influencing results. Furthermore there is no evidence of a dose response relationship with regard to ICS dose. A key issue with combination therapy is the excess risk of pneumonia conferred by the use of an ICS in this patient population. This risk does not appear to be proportional to the ICS dose but may differ between FP and budesonide. We conclude that further studies are required to identify the optimal dose of ICS, in terms of both risk and benefit, and to confirm their benefit in steroid naïve patients. Furthermore it will be important to determine whether the risk of pneumonia is apparent with both FP and budesonide and to identify factors which may predict steroid responsiveness in COPD.
The scientific rationale for combining long-acting β<inf>2</inf>-agonists and muscarinic antagonists in COPD
2010, Pulmonary Pharmacology and Therapeutics
Bronchodilators are the cornerstone of pharmacological management of COPD. For patients whose conditions are not sufficiently controlled by monotherapy, combining bronchodilators of different classes, in particular an inhaled muscarinic antagonist with an inhaled β₂-agonist, seems a convenient way of delivering treatment and obtaining superior results. When administered as combination therapy, short-acting bronchodilators provide superior bronchodilation compared with individual agents given alone. More recently, long-acting β₂-agonists (LABAs) and muscarinic antagonists (LAMAs) have been introduced, and current guidelines recommend regular use of these agents alone or as concurrent therapy in COPD to maximize bronchodilation. In particular, the combination of a LABA plus LAMA seems to play an important role. This article illustrates the scientific rationale for combining LABAs and LAMAs in COPD, reviews the clinical evidence to support these agents given in combination, and discusses their potential role in the management of patients with COPD.
Faster onset of action of formoterol versus salmeterol in patients with chronic obstructive pulmonary disease: A multicenter, randomized study
2009, Pulmonary Pharmacology and Therapeutics
Citation Excerpt :
The GOLD guidelines recommend the use of long-acting β2-adrenergic agonists (LABAs) and anticholinergic agents, either alone or in combination, for the treatment of moderate to very severe COPD [11]. Two currently available LABAs for the treatment of COPD are formoterol and salmeterol, which have demonstrated efficacy in patients with COPD when administered twice-daily (BID) [4,7,8,12–24]. In clinical studies, formoterol has demonstrated a more rapid onset of action than salmeterol, as measured by forced expiratory volume in 1 s (FEV1) [19,22,23].
Chronic obstructive pulmonary disease (COPD) is a growing public health problem that has increased in recent years. It similarly affects men and women, especially those who smoke. The goals of COPD pharmacotherapy are to improve lung function, reduce symptoms, prevent exacerbations, and improve patients' health status. Bronchodilators are the foundation of treatment for COPD, and the long-acting β₂-agonists formoterol and salmeterol are both indicated for regular use by patients with stable COPD.
A clinical study was conducted to compare the onset of bronchodilator effects following treatment with formoterol 12 μg administered twice-daily (BID) or salmeterol 50 μg BID. The trial also assessed whether the bronchodilator effects of treatment resulted in significant differences in clinical response.
This was a randomized, multicenter, open-label, parallel-group study of formoterol 12 μg BID versus salmeterol 50 μg BID, both administered for 28 days. Patients were current or previous smokers aged ≥40 years, with a diagnosis of stable COPD. The primary efficacy variable was change from baseline in forced expiratory volume in 1 s (FEV₁) 5 min after drug administration on day 28. Secondary efficacy variables included changes from baseline in the 6-min walk test (6MWT) and rescue medication use. The primary variable was assessed by analysis of covariance, with baseline FEV₁ as the covariate.
A total of 270 patients were randomized to formoterol 12 μg BID (n = 137) or salmeterol 50 μg BID (n = 133). In the intent-to-treat population the least square (LS) mean change from baseline in FEV₁ at 5 min postdose on day 28 was 0.13 L in the formoterol group compared with 0.07 L in the salmeterol group (P = 0.022). At 30 min postdose on day 28, the LS mean change from baseline in FEV₁ was 0.17 L in the formoterol group compared with 0.07 L in the salmeterol group (P < 0.001). Similar changes were reported at 60 min postdose (0.19 L for the formoterol group versus 0.13 L for the salmeterol group, P = 0.069). Patients in the formoterol group walked longer distances in the 6MWT and used less rescue medication compared with patients in the salmeterol group, although the differences were not statistically significant.
Significantly greater improvements from baseline in FEV₁ were observed at 5 and 30 min postdose with formoterol 12 μg compared with salmeterol 50 μg after 28 days of treatment. Numeric improvements in the 6MWT and rescue medication use were also observed with formoterol.
Quantitation of Formoterol, Salbutamol, and Salbutamol-4′-O-Sulfate in Human Urine and Serum via UHPLC-MS/MS
2023, Separations
Lung deposition of inhaled once-daily long-acting muscarinic antagonists via standard jet nebulizer or dry powder inhaler, measured using functional respiratory imaging, in patients with chronic obstructive pulmonary disease
2022, Therapeutic Advances in Respiratory Disease
A review of the efficacy and safety of fluticasone propionate/formoterol fixed-dose combination
2022, Expert Review of Respiratory Medicine

View all citing articles on Scopus

View full text

Regular ArticleEffect of Salmeterol and Formoterol in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Regular Article
Effect of Salmeterol and Formoterol in Patients with Chronic Obstructive Pulmonary Disease