Beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide: Synergy of triple combination therapy on human airway smooth muscle ex vivo.
Administration, Inhalation
Adrenergic beta-2 Receptor Agonists
Beclomethasone
/ pharmacology
Bronchodilator Agents
/ pharmacology
Drug Combinations
Drug Therapy, Combination
Formoterol Fumarate
/ therapeutic use
Glycopyrrolate
/ therapeutic use
Humans
Muscarinic Antagonists
/ pharmacology
Muscle, Smooth
Pulmonary Disease, Chronic Obstructive
/ drug therapy
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
27
05
2019
revised:
11
10
2019
accepted:
12
10
2019
pubmed:
30
10
2019
medline:
22
6
2021
entrez:
30
10
2019
Statut:
ppublish
Résumé
Combining inhaled corticosteroids (ICSs), long-acting β Human passively sensitized airways and bronchi from COPD donors were stimulated with histamine or carbachol. Tissues were incubated overnight with beclomethasone and then treated with formoterol and glycopyrronium, alone or in triple combination. The interaction was assessed by using Bliss Independence and Unified Theory theorems. Beclomethasone/formoterol/glycopyrronium combination synergistically relaxed medium bronchi and small airways. Beclomethasone/formoterol/glycopyrronium combination at 100:6:12.5 combination ratio was a balanced drug mixture leading to very strong synergistic effect on relaxation of medium bronchi (Combination Index: from 0.042 to 0.96) and middle to very strong synergy in small airways (Combination Index: from 0.018 to 0.310). The synergy was related with the activation of intracellular glucocorticoid receptors and G Triple beclomethasone/formoterol/glycopyrronium combination induces synergistic bronchorelaxant effect in medium and small human airways, at least in ex vivo experiments. Further research is needed to confirm these findings in clinical studies in patients with asthma or COPD.
Sections du résumé
BACKGROUND AND PURPOSE
Combining inhaled corticosteroids (ICSs), long-acting β
EXPERIMENTAL APPROACH
Human passively sensitized airways and bronchi from COPD donors were stimulated with histamine or carbachol. Tissues were incubated overnight with beclomethasone and then treated with formoterol and glycopyrronium, alone or in triple combination. The interaction was assessed by using Bliss Independence and Unified Theory theorems.
KEY RESULTS
Beclomethasone/formoterol/glycopyrronium combination synergistically relaxed medium bronchi and small airways. Beclomethasone/formoterol/glycopyrronium combination at 100:6:12.5 combination ratio was a balanced drug mixture leading to very strong synergistic effect on relaxation of medium bronchi (Combination Index: from 0.042 to 0.96) and middle to very strong synergy in small airways (Combination Index: from 0.018 to 0.310). The synergy was related with the activation of intracellular glucocorticoid receptors and G
CONCLUSION
Triple beclomethasone/formoterol/glycopyrronium combination induces synergistic bronchorelaxant effect in medium and small human airways, at least in ex vivo experiments. Further research is needed to confirm these findings in clinical studies in patients with asthma or COPD.
Identifiants
pubmed: 31660611
doi: 10.1111/bph.14909
pmc: PMC7042115
doi:
Substances chimiques
Adrenergic beta-2 Receptor Agonists
0
Bronchodilator Agents
0
Drug Combinations
0
Muscarinic Antagonists
0
Beclomethasone
KGZ1SLC28Z
Glycopyrrolate
V92SO9WP2I
Formoterol Fumarate
W34SHF8J2K
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1150-1163Informations de copyright
© 2019 The British Pharmacological Society.
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