Protection against methacholine bronchoconstriction to assess relative potency of inhaled beta2-agonist.
The purposes of this study were to estimate the relative dose potency (RP) of two formulations of salbutamol pressurized metered-dose inhalers (Proventil-HFA and Ventolin-CFC MDIs) to protect against methacholine bronchoconstriction, to validate this method and provide recommendations. The protective effects of 100-, 200-, and 400-micrograms doses of Proventil-HFA were compared with the same doses of Ventolin-CFC in 18 adult asthmatics (mean FEV1, 92% predicted; mean baseline PC20 methacholine, 1.8 mg/ml), in a dose-level blind, balanced, eight-period, crossover, placebo-controlled study. The log-transformed PC20 values after each dose of the drugs were compared by repeated-measures analysis of variance (ANOVA). A significant dose-effect was present (p < 0.0001). Using the Finney assay, the RP of Proventil-HFA compared with Ventolin-CFC was 1.08 (90% CI, 0.81-1.46) (80% power). This was also estimated using a nonlinear Emax model to validate the Finney method. The most precise estimate of RP was obtained with the comparison between 100- and 200-micrograms doses (RP, 1.00; 90% CI, 0.77-1.31). There were no adverse events resulting from the drugs or methacholine. We conclude that Proventil-HFA salbutamol is bioequivalent to Ventolin-CFC salbutamol. Bronchoprotection to methacholine is a valid method of demonstrating bioequivalence. By this method, 100- and 200-micrograms doses of salbutamol inhalations from an MDI will suffice.
Parameswaran
K N
KN
Asthma Research Group, Department of Medicine, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada.
Inman
M D
MD
Ekholm
B P
BP
Morris
M M
MM
Summers
E
E
O'Byrne
P M
PM
Hargreave
F E
FE
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D013810:Therapeutic Equivalency; D014797:Vital Capacity / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D016210:Methacholine Chloride; D000420:Albuterol