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- W1601071513 abstract "Background: AZD3199 is a novel, ultra long acting β 2 -agonist (uLABA) designed to combine 24 hour duration of action with a fast onset of action similar to formoterol, as well as low systemic exposure. Its in vivo profile was evaluated in the guinea pig. Methods: Bronchoconstriction was elicited in anesthetized guinea pigs by histamine administration. Dose-response curves for AZD3199 given via the inhaled and intra-tracheal (i.t.) routes were constructed and sub-maximal doses used to define duration of action from 2–72 hours. The b-antagonist propranolol was administered after histamine-challenge to show the level of β 2 efficacy at each dose and time point. Blood samples were taken throughout and plasma K + concentrations used as a marker of systemic β 2 effects. Satellite groups were used to monitor lung and plasma AZD3199 levels. The pharmacodynamic and pharmacokinetic profiles of AZD3199 were compared to formoterol and salmeterol. Results: Sub-maximal doses of AZD3199 given i.t. inhibited bronchoconstriction for 24 hours; equi-effective doses of formoterol and salmeterol had significant effects for 12 hours. AZD3199 had the longest lung PK half-life. Inhalation of sub-maximal doses of nebulized AZD3199 gave bronchoprotection lasting 24 hours, with no significant effects on blood K + levels. An equi-effective inhaled dose of formoterol bronchoprotected for 8 hours with decreases in blood K + seen at 2 hours. The reduced systemic effects for AZD3199 relative to formoterol are consistent with its high lung to plasma concentration ratio. Conclusion: AZD3199 is a novel uLABA with a fast onset of action and a longer duration of action than conventional LABAs, and also has a low potential for systemic effects." @default.
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- W1601071513 date "2011-09-01" @default.
- W1601071513 modified "2023-09-28" @default.
- W1601071513 title "AZD3199: A fast acting β2-receptor agonist with a long duration of action" @default.
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