Twelve-hour bronchodilation in asthma with a single aerosol dose of the anticholinergic compound glycopyrrolate.
Anticholinergic aerosols provide effective bronchodilation in some patients with obstructive lung disease. Glycopyrrolate is a quaternary ammonium anticholinergic compound that is poorly absorbed from mucus membranes, thus reducing anticholinergic side effects. In 20 adult patients with asthma, we evaluated bronchodilation to a single administration of metered-dose glycopyrrolate aerosol (GA) to ascertain its onset and duration of action along with evaluation of safety. In this randomized, double-blind, placebo-controlled, single-dose, crossover trial, bronchodilation was evaluated on five separate occasions to either placebo or a GA dose of 80, 240, 480, or 960 micrograms. Baseline spirometry for each patient on each visit was similar (mean FEV1 +/- SD of 62.2 +/- 13.6% predicted). After aerosol dosing, spirometry was measured at 30 minutes and then at hourly intervals up to 12 hours. Compared to placebo, metered-dose aerosols of 240, 480 and 960 micrograms elicited significantly greater bronchodilation at each test time. Furthermore, significant bronchodilation was noted within 30 minutes of dosing and was sustained for at least 12 hours. Bronchodilation with the 480 and 960 micrograms dose was equal, and both were greater than 240 micrograms. A subset of four asthma patients with baseline FEV1 values less than 50% predicted did not have a bronchodilating response with GA. No notable side effects occurred. Thus, a single aerosol dose of GA provides clinically significant, safe 12-hour bronchodilation in patients with asthma without severe airway obstruction (i.e., FEV1 greater than 50% predicted).
Schroeckenstein
D C
DC
University of Wisconsin Medical School, Madison.
Bush
R K
RK
Chervinsky
P
P
Busse
W W
WW
D000328:Adult; D000336:Aerosols; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D011759:Pyrrolidines / Q000008:administration & dosage*; D013610:Tachycardia / Q000139:chemically induced
D000336:Aerosols; D011759:Pyrrolidines; D006024:Glycopyrrolate