Long-acting bronchodilation with once-daily dosing of tiotropium (Spiriva)in stable chronic obstructive pulmonary disease

Tiotropium (Spiriva; Ba679BR) is a new-generation, long-acting anticholiner gic bronchodilator that has muscarinic M-1 and M-3 receptor subtype selecti vity. A multicenter, randomized, double-blind, parallel group, placebo-cont rolled study was conducted to evaluate the dose-response characteristics of tiotropium inhalation powder given once daily to stable patients with chro nic obstructive pulmonary disease (COPD). Patients (mean FEV1 = 1.08 L [42% predicted]) were randomized to receive 0, 4.5, 9, 18, or 36 mu g tiotropiu m once daily at noon for 4 wk, with spirometry done before and hourly for 6 h after dosing. Patients measured and recorded their peak expiratory flow rates (PEFRs) three times each day. Significant dose-related improvement in FEV1 and significant improvement in FVC occurred within 1 h after the firs t dose of tiotropium as compared with placebo. Over the 29 d of the study, all doses of tiotropium produced significant increases over placebo in trou gh (i.e, as measured spirometrically at 20 to 24 h after the previous dose and just before the next dose of tiotropium), peak, and 6-h postdose averag e FEV1 and FVC, and in PEFR, without a significant difference among the dif ferent doses investigated. PEFR gradually returned to pretreatment baseline levels over a 3-wk evaluation period following the discontinuation of tiot ropium. The overall safety profile far the tiotropium doses was, similar to that for placebo. In summary, tiotropium was shown to be safe and effectiv e in doses ranging from 4.5 to 36 mu g delivered once daily. The improvemen ts in spirometry with once-daily dosing confirm the long duration of action of tiotropium reported in single-dose studies, and its sustained improveme nt of spirometric measures over the 1 mo of testing in the study points to utility of tiotropium as a maintenance bronchodilator for patients with COP D. On the basis of the comparable bronchodilator response at doses from 9 t o 36 mu g, and advantages suggested by the safely profile at doses below 36 mu g In this study, a dose of 18 mu g once daily was selected for use in l ong-term studies of the safety and efficacy of tiotropium.