Use of bronchial provocation with histamine to compare the pharmacodynamics of inhaled albuterol and metaproterenol in patients with asthma.
Because measurement of effects on airway responsiveness may have advantages over the study of bronchodilatation for the evaluation of the effects of inhaled beta 2-agents, we developed a method using airway responsiveness for the independent quantitation of the relative potencies and rates of decline in effect of these drugs. This methodology was applied to the evaluation and comparison of inhaled metaproterenol and albuterol. The effects of two different doses of each drug (one and two inhalations of albuterol and two and four inhalations of metaproterenol from commercially available metered-dose inhalers) were compared with a double-blind, randomized, placebo-controlled, crossover study of 13 subjects. The effects of metaproterenol and albuterol declined at rates that were not significantly different. However, based on the effects on activity ratio at 30 minutes, each puff of metaproterenol was an estimated 0.37 times as potent as each puff of albuterol (95% confidence limits, 0.22 to 0.52). In recommended two puff doses, measurable effects of albuterol persisted longer than effects of metaproterenol. However, this appears to be because of a greater initial effectiveness of two puffs of albuterol rather than differences in the rates at which the effects of the two drugs declined with time. Airway responsiveness thus appears to be a useful tool for evaluating inhaled beta 2-agonists and designing beta 2-agonist dosing regimens.
Ahrens
R C
RC
Harris
J B
JB
Milavetz
G
G
Annis
L
L
Ries
R
R
D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000378:metabolism / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001985:Bronchial Provocation Tests; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine; D006801:Humans; D007700:Kinetics; D008297:Male; D009921:Metaproterenol / Q000378:metabolism / Q000627:therapeutic use*
D009921:Metaproterenol; D006632:Histamine; D000420:Albuterol