Little is known about the impact of COPD on lung deposition of inhaled drugs and the relationship between lung-dose and response of pulmonary function measurements.

Nineteen patients with varying degrees of COPD were randomized to inhale single doses of formoterol (Oxis^®) Turbuhaler^® 4.5, 9, 18, and 36μg in a double blind, placebo-controlled, crossover design. Urinary excreted formoterol during 32h was used to determine absolute lung deposition. Peak inspiratory flow (PIF) and inhaled volume (IV) were recorded to assess the patients’ ability to use Turbuhaler. Efficacy was measured by spirometry, inspiratory capacity (IC), airway conductance (sG_AW), and absolute lung volumes.

Mean pulmonary bioavailability of formoterol was about 24% of the nominal delivered dose after inhalation for the different treatments. No significant correlations between lung deposition and baseline FEV₁, PIF or IV were shown. All formoterol doses produced statistically significant increases in FEV₁, FVC, IC, and sG_AW relative to placebo. Linear dose/response relationships were observed for these variables, with more narrow limits of the slopes for the lung-dose/response relationships than for the nominal-dose/response relationships. Moreover, 36 and 18μg formoterol statistically significantly decreased functional residual capacity (FRC) and residual volume (RV) relative to placebo.

This study could not show any difference in lung deposition of formoterol inhaled via Turbuhaler between patients with moderate and severe COPD. Moreover, the effect of formoterol on various pulmonary function measurements were more closely related to lung deposition than the inhaled nominal dose.