1. Salmeterol Xinafoate
2. Serevent
3. Xinafoate, Salmeterol
1. 89365-50-4
2. Serevent
3. Astmerole
4. Aeromax
5. Salmeterolum [latin]
6. 2-(hydroxymethyl)-4-[1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl]phenol
7. Gr 33343x
8. Salmaterol
9. Sn408d
10. 2-(hydroxymethyl)-4-(1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl)phenol
11. Gr 33343 X
12. 2i4bc502bt
13. Chebi:64064
14. Gr-33343-x
15. Salmeterol Fluticasone Propionate Mixture
16. Salmeterolum
17. 4-(1-hydroxy-2-(6-(4-phenylbutoxy)hexylamino)ethyl)-2-(hydroxymethyl)phenol
18. 2-(hydroxymethyl)-4-[1-hydroxy-2-({6-[(4-phenylbutyl)oxy]hexyl}amino)ethyl]phenol
19. 4-(1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl)-2-(hydroxymethyl)phenol
20. Smr000466295
21. Hsdb 7315
22. Sr-01000076139
23. Salmeterol (usan/inn)
24. Unii-2i4bc502bt
25. Salmeterol [usan:inn:ban]
26. Ncgc00025247-01
27. Fluticasonepropiponate
28. (+-)-4-hydroxy-alpha'-(((6-(4-phenylbutoxy)hexyl)amino)methyl)-m-xylene-alpha,alpha'-diol
29. (+-)-4-hydroxy-alpha1-(((6-(4-phenylbutoxy)hexyl)amino)methyl)-1,3-benzenedimethanol
30. Cpd000466295
31. Salmeterol [mi]
32. Salmeterol [inn]
33. Prestwick3_000945
34. Salmeterol Dimer Impurity
35. Salmeterol [hsdb]
36. Salmeterol [usan]
37. Dsstox_cid_3571
38. Salmeterol [vandf]
39. S 2692
40. Schembl4767
41. Chembl1263
42. Dsstox_rid_77087
43. Salmeterol [who-dd]
44. Dsstox_gsid_23571
45. Lopac0_001100
46. Bspbio_000910
47. Gtpl559
48. Mls000759000
49. Mls001424322
50. Salmeterol Related Compound H
51. Bpbio1_001002
52. Salmeterol Xinafoate Impurity 1
53. Dtxsid6023571
54. Bdbm25771
55. Hms2052h13
56. Hms2090e17
57. Hms2097n12
58. Hms3268k19
59. Hms3394h13
60. Hms3412p13
61. Hms3714n12
62. Hms3886g10
63. Amy37616
64. Bcp04199
65. Ex-a4409
66. Gr33343xgr33343x
67. Tox21_113584
68. Mfcd00867037
69. S5527
70. Stk629186
71. Akos005561914
72. Ccg-101194
73. Ccg-205176
74. Db00938
75. Nc00444
76. Sdccgsbi-0633788.p001
77. 1,3-benzenedimethanol, 4-hydroxy-.alpha.1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-
78. 1,3-benzenedimethanol, 4-hydroxy-alpha1-(((6-(4-phenylbutoxy)hexyl)amino)methyl)-, (+-)-
79. Mrf-0000468
80. Ncgc00015938-03
81. Ncgc00025247-02
82. 1,3-benzenedimethanol, 4-hydroxy-alpha(sup 1)-(((6-(4-phenylbutoxy)hexyl)amino)methyl)-, (+-)-
83. 1,3-benzenedimethanol, 4-hydroxy-alpha(sup 1)-(((6-(4-phenylbutoxy)hexyl)amino)methyl-, (+-)-
84. As-56157
85. Hy-14302
86. Salmeterol 100 Microg/ml In Acetonitrile
87. Cas-89365-50-4
88. Ab00513972
89. Ft-0674508
90. Ft-0674509
91. C07241
92. C77008
93. D05792
94. Ab00513972-07
95. 365s504
96. En300-18530979
97. L000532
98. Q424333
99. Salmeterol Impurity H (xinafoate Adduct Impurity)
100. Q-101428
101. Sr-01000076139-2
102. Sr-01000076139-6
103. Brd-a01320529-001-05-9
104. 2-hydroxymethyl-4-{1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl}phenol
105. 5-[2-[6-(4-phenylbutoxy)hexylamino]-1-hydroxyethyl]-2-hydroxybenzenemethanol
106. ( Inverted Question Mark) 4-hydroxy-a1-[[[6-(4-phenylbutoxy)hexyl]amino]m-ethyl]-1,3-benzenedimethanol; Gr 33343x
107. 1-hydroxy-2-naphthoic Acid;4-[1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl]-2-methylol-phenol
| Molecular Weight | 415.6 g/mol |
|---|---|
| Molecular Formula | C25H37NO4 |
| XLogP3 | 3.9 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 16 |
| Exact Mass | g/mol |
| Monoisotopic Mass | g/mol |
| Topological Polar Surface Area | 82 |
| Heavy Atom Count | 30 |
| Formal Charge | 0 |
| Complexity | 403 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
Bronchodilator
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 1497
Salmeterol ... /is/ indicated to prevent bronchospasm and reduce the frequency of acute asthma exacerbations in patients with chronic asthma who require regular treatment with an inhaled shorter-acting beta-adrenergic bronchodilator. ... Salmeterol may be used with or without concurrent inhaled or systemic corticosteroid therapy. During therapy with salmeterol ... , it is important for patients to have a fast-acting inhaled beta-adrenergic bronchodilator available for relief of acute attacks. /Included in US product labeling/
Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004., p. 604
Salmeterol ... /is/ indicated for the prevention of exercise-induced bronchospasm. With use of salmeterol ... , it is important for patients to also have a fast-acting inhaled beta-adrenergic bronchodilator available for relief of acute attacks. ... /Included in US product labeling/
Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004., p. 604
Salmeterol ... /is/ indicated as bronchodilators for the treatment of bronchospasm associated with chronic obstructive airway disease, including bronchitis and pulmonary emphysema. ... /Included in US product labeling/
Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004., p. 604
Data from a large placebo-controlled safety study that was stopped early suggest that salmeterol may be associated with rare serious asthma episodes or asthma-related deaths. Data from this study, called the Salmeterol Multi-center Asthma Research Trial (SMART), further suggest that the risk might be greater in African American patients. These results led to stopping the study prematurely. The data from the SMART study are not adequate to determine whether concurrent use of inhaled corticosteroids provides protection from this risk. Given the similar basic mechanisms of action of beta2-agonists, it is possible that the findings seen in the SMART study may be consistent with a class effect. Findings similar to the SMART study findings were reported in a prior 16-week clinical study performed in the United Kingdom, the Salmeterol Nationwide Surveillance (SNS) study. In the SNS study, the incidence of asthma-related death was numerically, though not statistically, greater in patients with asthma treated with salmeterol (42 ug twice daily) versus albuterol (180 ug 4 times daily) added to usual asthma therapy.
Physicians Desk Reference. 58th ed. Thomson PDR. Montvale, NJ 2004., p. 1617
Salmeterol oral inhalation therapy is intended for the maintenance treatment of asthma or chronic obstructive pulmonary disease (COPD) and should not be initiated in patients with substantially worsening or acutely deteriorating asthma or acute symptoms of COPD. ... Serious acute respiratory events, including fatalities, have been reported when salmeterol oral inhalation therapy has been initiated in such situations. In most cases, these adverse events have occurred in patients with severe asthma (e.g., those with a history of corticosteroid dependence, low pulmonary function, intubation, mechanical ventilation, frequent hospitalizations, or previous life-threatening acute asthma exacerbations) and/or in some patients in whom asthma has been acutely deteriorating (e.g., unresponsive to usual medications, increasing need for inhaled short-acting beta-agonists, marked increase in symptoms, recent emergency room visits, sudden or progressive deterioration in pulmonary function). However, such events also have occurred in patients with less severe asthma. Although it has not been determined whether salmeterol oral inhalation therapy contributed to these events or simply failed to relieve the deteriorating asthma, the manufacturer states that use of salmeterol oral inhalation in patients with substantially worsening or acutely deteriorating asthma is inappropriate.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 1313
Since salmeterol is cleared predominantly by hepatic metabolism, impaired liver function theoretically may lead to accumulation of the drug in plasma. Therefore, the manufacturer recommends that patients with hepatic disease be monitored closely while receiving salmeterol therapy.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 1311
Usual doses of salmeterol oral inhalation generally produce no apparent cardiovascular effects. However, clinically important changes in systolic and/or diastolic blood pressure and heart rate, as well as ECG changes, have occurred infrequently with salmeterol therapy in controlled clinical studies. Adverse cardiovascular effects of salmeterol have in some instances required discontinuance of the drug. Hypertension has been reported with salmeterol inhalation aerosol or powder during postmarketing surveillance.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 1311
For more Drug Warnings (Complete) data for SALMETEROL (21 total), please visit the HSDB record page.
Salmeterol is indicated in the treatment of asthma with an inhaled corticosteroid, prevention of exercise induced bronchospasm, and the maintenance of airflow obstruction and prevention of exacerbations of chronic obstructive pulmonary disease.
FDA Label
Adrenergic beta-2 Receptor Agonists
Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS. (See all compounds classified as Adrenergic beta-2 Receptor Agonists.)
Bronchodilator Agents
Agents that cause an increase in the expansion of a bronchus or bronchial tubes. (See all compounds classified as Bronchodilator Agents.)
R03AC12
S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355
R - Respiratory system
R03 - Drugs for obstructive airway diseases
R03A - Adrenergics, inhalants
R03AC - Selective beta-2-adrenoreceptor agonists
R03AC12 - Salmeterol
Absorption
In asthmatic patients, a 50g dose of inhaled salmeterol powder reaches a Cmax of 47.897pg/mL, with a Tmax of 0.240h, and an AUC of 156.041pg/mL/h.
Route of Elimination
Salmeterol is 57.4% eliminated in the feces and 23% in the urine. Less than 5% of a dose is eliminated in the urine as unchanged salmeterol.
Volume of Distribution
In asthmatic patients, the volume of distribution of the central compartment is 177L and the volume of distribution of the peripheral compartment is 3160L.
Clearance
The average clearance of salmeterol in a group of asthmatic patients was 392L/h. Further data regarding the clearance of salmeterol is not readily available.
The absorption of salmeterol xinafoate from the respiratory tract following oral inhalation has not been fully characterized. Although it has been suggested that most of an orally inhaled drug actually is swallowed, the bronchodilating action of orally inhaled sympathomimetic agents is believed to result from a local action of the portion of the dose that reaches the bronchial tree. Systemic concentrations of salmeterol are low or undetectable after inhalation of the recommended dosage of the aerosol (42 ug) or powder (50 ug) twice daily and are not predictive of therapeutic effects.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 1316
Binding of salmeterol averages 96% in vitro to human plasma proteins over the concentration range of 8-7722 ng/mL, which are concentrations greatly exceeding those achieved following usual doses of the drug. Salmeterol is bound to albumin and alpha 1 acid glycoprotein; the xinafoate moiety also is highly protein bound (greater than 99%) to albumin.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 1317
The distribution of salmeterol into various human organs and tissues following oral inhalation has not been fully characterized. Results of studies in rats indicate that salmeterol crosses the blood-brain barrier in trace amounts.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 1317
It is not known if salmeterol and/or its metabolites cross the placenta in humans. Following oral administration of 10 mg/kg of salmeterol in mice and rats, placental transfer of salmeterol occurred.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 1317
For more Absorption, Distribution and Excretion (Complete) data for SALMETEROL (8 total), please visit the HSDB record page.
Salmeterol is predominantly metabolized by CYP3A4 to alpha-hydroxysalmeterol, and minorly by an unknown mechanism to an O-dealkylated metabolite.
... A minor metabolite is formed by o-dealkylation of the phenylalkyl side chain /of salmeterol/.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 1317
... The cytochrome P450 (CYP) isoform 3A4 is responsible for aliphatic oxidation of salmeterol base, which is extensively metabolised by hydroxylation with the major metabolite being alpha-hydroxysalmeterol, with subsequent elimination predominantly in the feces...
PMID:11825095 Cazzola M et al; Clin Pharmacokinet 41 (1): 19-30 (2002)
Hepatic, metabolized by hydroxylation via CYP3A4 Half Life: 5.5 hours
The half life of salmeterol is 5.5h.
Following oral administration of salmeterol in healthy individuals, the terminal elimination half-lives of salmeterol and the xinafoate moiety are about 5.5 hours and 11-15 days, respectively.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 1317
Beta-2 adrenoceptor stimulation causes relaxation of bronchial smooth muscle, bronchodilation, and increased airflow. Salmeterol is hypothesized to bind to 2 sites on the beta-2 adrenoceptor. The saligenin moiety binds to the active site of the beta-2 adrenoceptor. The hydrophilic tail of salmeterol binds to leucine residues in the exo-site of the beta-2 adrenoceptor almost irreversibly, allowing salmeterol to persist in the active site, which is responsible for it's long duration of action. Another hypothesis is that the lipophilic drug diffuses into lipid bilayer of smooth muscle cells and provides a depot of drug to the cells over a longer period of time.
In vitro tests show that salmeterol is a potent and long-lasting inhibitor of the release of mast cell mediators, such as histamine, leukotrienes, and prostaglandin D2, from human lung. Salmeterol inhibits histamine-induced plasma protein extravasation and inhibits platelet activating factor-induced eosinophil accumulation in the lungs of guinea pigs when administered by the inhaled route. In humans, single doses of salmeterol attenuate allergen-induced bronchial hyper-responsiveness.
Physicians Desk Reference. 58th ed. Thomson PDR. Montvale, NJ 2004., p. 1615
The pharmacologic effects of beta2-adrenoceptor agonist drugs, including salmeterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.
Physicians Desk Reference. 58th ed. Thomson PDR. Montvale, NJ 2004., p. 1615
Salmeterol is a long-acting beta-adrenergic agonist. In vitro studies and in vivo pharmacologic studies demonstrate that salmeterol is selective for beta2-adrenoceptors compared with isoproterenol, which has approximately equal agonist activity on beta1- and beta2-adrenoceptors. In vitro studies show salmeterol to be at least 50 times more selective for beta2-adrenoceptors than albuterol. Although beta2-adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-adrenoceptors are the predominant receptors in the heart, there are also beta2-adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. The precise function of these is not yet established, but they raise the possibility that even highly selective beta2-agonists may have cardiac effects.
Physicians Desk Reference. 58th ed. Thomson PDR. Montvale, NJ 2004., p. 1615
Salmeterol ... membrane binding is non-competitive and dissociation is slow so that its effects last for many hours. Despite this, salmeterol does not accumulate in tissues. Its mechanism of action can be explained by binding to a specific exo-site domain of the beta 2-receptor protein to produce continuous stimulation of the active site of the receptor, which gives salmeterol a profile of pharmacological activity unlike that of other beta 2-agonists. Due to its potent and prolonged activation of beta 2-adrenoceptors in airway smooth muscle cells, endothelial cells, mast cells and epithelial cells, salmeterol induces prolonged bronchodilatation, reduced vascular permeability, inhibition of inflammatory mediators, stimulation of ciliary function and modulation of ion and water transport across the bronchial mucosa.
PMID:8099695 Johnson M et al; Life Sci 52 (26): 2131-43 (1993)
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