Plethysmography and impulse oscillometry assessment of tiotropium and ipratropium bromide; a randomized, double-blind, placebo-controlled, cross-over study in healthy subjects.
OBJECTIVE
Spirometry, plethysmography and impulse oscillometry (IOS) measure different aspects of lung function. These methods have not been compared for their ability to assess long- and short-acting anticholinergic agents. We therefore performed a double-blind, placebo-controlled, four-way cross-over study in 30 healthy subjects.


METHODS
Single doses of tiotropium bromide (Tio) 54 and 18 mcg, ipratropium bromide (IB) 40 mcg and placebo were administered. Specific conductance (sGaw), total lung capacity (TLC), inspiratory capacity (IC) and residual volume (RV) were measured using plethysmography, while IOS measured resistance (R5-25) and reactance (RF and X5). Pulmonary function was measured for 26 h post dose.


RESULTS
Tio caused significant improvements in sGaw, forced expiratory voume in 1 s (FEV(1)), maximum mid-expiratory flow (MMEF) and R5-R25 at time points up to 26 h, with no clear differences between doses. IB improved the same parameters, but only up to 8 h. The weighted mean change (0-24 h) caused by Tio 54 mcg compared with placebo for FEV(1) was 240 ml (95% confidence interval 180, 300), while for sGaw the ratio of geometric means (Tio compared with placebo) was 1.35 (1.28, 1.41). Neither drug caused consistent statistically significant changes in RF, forced vital capacity, TLC or IC over 26 h. RV was significantly improved from 8 to 24 h by Tio 54 mcg only.


CONCLUSIONS
In addition to spirometry, IOS resistance measurements and sGaw can distinguish between the effects of long- and shortacting anticholinergic effects in healthy subjects.
Medicines Evaluation Unit, North-west Lung Research Centre, Manchester, UK. dsingh@meu.org.uk
D
D
Singh
R
R
Tal-Singer
I
I
Faiferman
S
S
Lasenby
A
A
Henderson
D
D
Wessels
A
A
Goosen
N
N
Dallow
R
R
Vessey
M
M
Goldman
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005540:Forced Expiratory Flow Rates / Q000187:drug effects / Q000502:physiology; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009241:Ipratropium / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009991:Oscillometry / Q000379:methods*; D010991:Plethysmography / Q000379:methods*; D012115:Residual Volume / Q000187:drug effects / Q000502:physiology; D012602:Scopolamine Derivatives / Q000494:pharmacology*; D013147:Spirometry / Q000379:methods; D000069447:Tiotropium Bromide; D014109:Total Lung Capacity / Q000187:drug effects / Q000502:physiology
D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D009241:Ipratropium; D000069447:Tiotropium Bromide