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Pulm Pharmacol Ther. 2008 Aug;21(4):657-62. doi: 10.1016/j.pupt.2008.03.003. Epub 2008 Apr 7.

A pharmacokinetic/pharmacodynamic study comparing arformoterol tartrate inhalation solution and racemic formoterol dry powder inhaler in subjects with chronic obstructive pulmonary disease.

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Sepracor Inc., Marlborough, MA, USA.



Arformoterol is a single-isomer (R,R-formoterol) nebulized long-acting beta(2)-agonist approved for use in patients with chronic obstructive pulmonary disease (COPD). Exposure (plasma concentrations of (R,R)-formoterol) and forced expiratory volume in 1s (FEV(1)) were compared for 15 microg nebulized arformoterol and 12 and 24 microg racemic formoterol (containing 6 and 12 microg (R,R)-formoterol, respectively) delivered by dry powder inhaler (DPI).


An open-label, randomized, three-way crossover study in 39 subjects with COPD (FEV(1) 1.4L, 44.4% predicted). Twice-daily treatments included nebulized arformoterol (15 microg) and racemic formoterol DPI (12 and 24 microg) for 14 days. Plasma concentrations of (R,R)- and (S,S)-formoterol were determined on days 1 and 14 of each treatment period. Airway function efficacy endpoints included the percent change in trough FEV(1) from baseline on day 14 of each treatment period.


At steady state, exposure to (R,R)-formoterol was similar following nebulized 15 microg arformoterol (C(max): 6.5 pg/mL; AUC(0-tau): 56.5 pgh/mL) and 12 microg racemic formoterol DPI (C(max): 6.2 pg/mL; AUC((0-)(tau)()): 46.3 pgh/mL). The geometric mean ratios between these two treatments (90% confidence intervals) for C(max) and AUC((0-)(tau)()) were 0.91 (0.76, 1.09) and 1.16 (1.00, 1.35), respectively. Treatment with 24 microg racemic formoterol DPI resulted in dose proportionally higher (R,R)-formoterol: C(max) (10.8 pg/mL) and AUC((0-)(tau)()) (83.6 pgh/mL). Detectable (S,S)-formoterol was consistently measured only after treatment with racemic formoterol. The mean percent increase in trough FEV(1) was 19.1% in the arformoterol group, and 16.0% and 18.2% in the 12 and 24 microg racemic formoterol groups, respectively. Changes in (R,R)-formoterol concentrations over time paralleled changes in FEV(1).


In this study, plasma exposure to (R,R)-formoterol was similar for nebulized 15 microg arformoterol and 12 microg racemic formoterol DPI, and 40% lower than 24 microg racemic formoterol DPI. There was no evidence of chiral interconversion following treatment with arformoterol. Finally, temporal changes in airway function in all treatment groups corresponded to changes in (R,R)-formoterol plasma concentrations.

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