PROLONGED EFFECT OF TIOTROPIUM BROMIDE ON METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN ASTHMA

Inhaled anticholinergic drugs are effective in the treatment of chroni c obstructive pulmonary diseases (COPD), of acute asthma, and of some patients with nocturnal asthma. Tiotropium bromide (tiotropium) is a n ovel anticholinergic agent with a long duration of action and kinetic selectivity for M(1) and M(3)-subtypes of muscarinic receptors. We inv estigated the duration of protection of a single dose of inhaled tiotr opium against methacholine-induced bronchoconstriction in 12 male atop ic asthmatic volunteers in a double-blind, placebo-controlled study. O n four separate occasions 8 to 24 d apart, methacholine PC20 was measu red serially for up to 48 h after placebo and after three doses of tio tropium (10, 40, and 80 mu g). Each dose of tiotropium produced mild b ronchodilatation as measured by an increase in FEV(1) of between 5.5 a nd 11.1% from baseline, that was sustained for 24 h. There was signifi cant dose-dependent protection against methacholine challenge at 2 h o f 5.0 +/- 1.1, 7.1 +/- 0.5, and 7.9 +/- 0.7 (mean +/- SEM) doubling do ses after 10, 40, and 80 mu g respectively, and this persisted for 48 h. There were no adverse effects reported at any dose. The prolonged b ronchodilator response and protection against methacholine challenge s uggest that tiotropium may be useful in the treatment of COPD and noct urnal asthma and that once-daily dosing may be sufficient.