Protection against methacholine bronchoconstriction to assess relative potency of inhaled beta(2)-agonist

The purposes of this study were to estimate the relative dose potency (RP) of two formulations of salbutamol pressurized metered-dose inhalers (Proven til-HFA and Ventolin-CFC MDIs) to protect against methacholine bronchoconst riction, to validate this method and provide recommendations. The protectiv e effects of 100-, 200-, and 400-mu g 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 bli nd, balanced, eight-period, crossover, placebo-controlled study. The log-tr ansformed PC20 values after each dose of the drugs were compared by repeate d-measures analysis of variance (ANOVA). A significant dose-effect was pres ent (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 e stimated using a nonlinear E-max model to validate the Finney method. The m ost precise estimate of RP was obtained with the comparison between 100- an d 200-mu g doses (RP, 1.00; 90% CI, 0.77-1.31). There were no adverse event s resulting from the drugs or methacholine. We conclude that Proventil-HFA salbutamol is bioequivalent to Ventolin-CFC salbutamol. Bronchoprotection t o methacholine is a valid method of demonstrating bioequivalence. By this m ethod, 100 and 200-mu g doses of salbutamol inhalations from an MDI will su ffice.