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

被引:156
作者
Littner, MR
Ilowite, JS
Tashkin, DP
Friedman, M
Serby, CW
Menjoge, SS
Witek, TJ
机构
[1] Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care & Nursing Home, Sepulveda, CA USA
[2] Univ Calif Los Angeles, Sch Med, Div Pulm, Los Angeles, CA USA
[3] Winthrop Univ Hosp, Div Pulm, Mineola, NY 11501 USA
[4] Tulane Univ, Med Ctr, Sect Pulm Dis Crit Care & Environm Med, New Orleans, LA USA
[5] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA
关键词
D O I
10.1164/ajrccm.161.4.9903044
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Tiotropium (Spiriva; Ba679BR) is a new-generation, long-acting anticholinergic bronchodilator that has muscarinic M-1 and M-3 receptor subtype selectivity. A multicenter, randomized, double-blind, parallel group, placebo-controlled study was conducted to evaluate the dose-response characteristics of tiotropium inhalation powder given once daily to stable patients with chronic 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 tiotropium 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 first dose of tiotropium as compared with placebo. Over the 29 d of the study, all doses of tiotropium produced significant increases over placebo in trough (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 average FEV1 and FVC, and in PEFR, without a significant difference among the different doses investigated. PEFR gradually returned to pretreatment baseline levels over a 3-wk evaluation period following the discontinuation of tiotropium. The overall safety profile far the tiotropium doses was, similar to that for placebo. In summary, tiotropium was shown to be safe and effective in doses ranging from 4.5 to 36 mu g delivered once daily. The improvements in spirometry with once-daily dosing confirm the long duration of action of tiotropium reported in single-dose studies, and its sustained improvement of spirometric measures over the 1 mo of testing in the study points to utility of tiotropium as a maintenance bronchodilator for patients with COPD. On the basis of the comparable bronchodilator response at doses from 9 to 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 long-term studies of the safety and efficacy of tiotropium.
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页码:1136 / 1142
页数:7
相关论文
共 18 条
[1]   EXACT INFERENCE FOR CONTINGENCY-TABLES WITH ORDERED CATEGORIES [J].
AGRESTI, A ;
MEHTA, CR ;
PATEL, NR .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1990, 85 (410) :453-458
[2]  
BONE R, 1994, CHEST, V105, P1411
[3]  
CELLI BR, 1995, AM J RESP CRIT CARE, V152, pS77
[4]  
Chodosh S, 1999, AM J RESP CRIT CARE, V159, pA524
[5]   BA 679 BR, A NOVEL LONG-ACTING ANTICHOLINERGIC BRONCHODILATOR [J].
DISSE, B ;
REICHL, R ;
SPECK, G ;
TRAUNECKER, W ;
ROMINGER, KL ;
HAMMER, R .
LIFE SCIENCES, 1993, 52 (5-6) :537-544
[6]  
FERGUSON GT, 1993, NEW ENGL J MED, V328, P1017
[7]  
MAESEN FPV, 1993, EUR RESPIR J, V6, P1031
[8]  
MAESEN FPV, 1995, EUR RESPIR J, V8, P1506
[9]   Efficacy of salmeterol xinafoate in the treatment of COPD [J].
Mahler, DA ;
Donohue, JF ;
Barbee, RA ;
Goldman, MD ;
Gross, NJ ;
Wisniewski, ME ;
Yancey, SW ;
Zakes, BA ;
Rickard, KA ;
Anderson, WH .
CHEST, 1999, 115 (04) :957-965
[10]   15-YEAR INTERVAL SPIROMETRIC EVALUATION OF THE OREGON PREDICTIVE EQUATIONS [J].
MORRIS, JF ;
KOSKI, A ;
TEMPLE, WP ;
CLAREMONT, A ;
THOMAS, DR .
CHEST, 1988, 93 (01) :123-127