Formoterol and beclomethasone dipropionate interact positively in antagonising bronchoconstriction and inflammation in the lung.
These studies were designed to assess the pharmacodynamic interaction between formoterol and beclomethasone dipropionate (BDP) in controlling the bronchoconstriction and inflammatory response induced by various challenges in guinea-pigs and rats. In anaesthetised guinea-pigs, superfusion of the formoterol/BDP combination into the tracheal lumen had significantly more effect than the single components in antagonising the bronchoconstricting and inflammatory responses to acetylcholine or ovalbumin in a standard model of airway hyper-responsiveness. After ovalbumin challenge, the combination completely protected animals from death at doses lower than those effective when given separately. The combination, at doses ineffective individually, even counteracted the development of lung oedema induced by sephadex in the rat. Finally, in tracheal strips from ovalbumin-sensitised guinea-pigs pre-treatment with BDP (30 mg kg(-1) i.m.) completely reversed the rightward shift of the formoterol dose-response curve due to beta(2)-receptor desensitisation. In conclusion, these results indicate that formoterol and BDP together induce a favourable pharmacodynamic interaction which can be considered more than additive, at least in these experimental settings.
Razzetti
Roberta
R
Department of Pharmacology, Chiesi Farmaceutici S.p.A., Via Palermo 26/A, 43100 Parma, Italy. r.razzetti@chiesigroup.com
Bergamaschi
Marco
M
Villetti
Gino
G
Bolzoni
Piertonino
P
Civelli
Maurizio
M
Berti
Ferruccio
F
Rossoni
Giuseppe
G
D000109:Acetylcholine; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001507:Beclomethasone / Q000494:pharmacology* / Q000627:therapeutic use; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003911:Dextrans; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D010047:Ovalbumin; D011654:Pulmonary Edema / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D003911:Dextrans; D004338:Drug Combinations; D004983:Ethanolamines; D018343:Receptors, Adrenergic, beta-2; D010047:Ovalbumin; C025614:sephadex; D001507:Beclomethasone; D000109:Acetylcholine; D000420:Albuterol; D000068759:Formoterol Fumarate