Lung deposition and efficacy of inhaled formoterol in patients with moderate to severe COPD.
BACKGROUND
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.


METHODS
Nineteen patients with varying degrees of COPD were randomized to inhale single doses of formoterol (Oxis) Turbuhaler 4.5, 9, 18, and 36 microg in a double blind, placebo-controlled, crossover design. Urinary excreted formoterol during 32 h 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.


RESULTS
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 FEV(1), PIF or IV were shown. All formoterol doses produced statistically significant increases in FEV(1), 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 18 microg formoterol statistically significantly decreased functional residual capacity (FRC) and residual volume (RV) relative to placebo.


CONCLUSIONS
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.
Derom
Eric
E
Department of Respiratory Diseases, Ghent University Hospital, De Pintelaan 185, B 9000 Ghent, Belgium. eric.derom@Ugent.be
Strandgården
Kerstin
K
Schelfhout
Vanessa
V
Borgström
Lars
L
Pauwels
Romain
R
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008176:Lung Volume Measurements; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068759:Formoterol Fumarate