Dose-response protective effect of salbutamol on methacholine airway responsiveness using pressurized metered dose inhalers and Turbuhalers

Abstract

The purpose of this study was to estimate the relative dose potency of salbutamol Turbuhaler compared with salbutamol pressurized metered dose inhaler (pMDI) with respect to the protective effect against methacholine bronchoconstriction. Twenty-three asthmatic subjects with stable asthma participated in the study. Baseline forced expiratory volume in 1 s (FEV1) was 70% or more of predicted, and baseline methacholine provocative concentration causing a 20% fall in FEV1 (PC20) was 4 mg/mL or less. The design was randomized, double-blind, double-dummy, crossover and placebo controlled and was conducted over seven study days. On each study day, the subjects inhaled 50 μg or 100 μg of salbutamol via Turbuhaler, 100 μg, 200 μg, 400 μg or 800 μg of salbutamol via pMDI, or placebo in randomized order. PC20 was determined 30 mins after inhalation. Increasing doses of salbutamol pMDI increased the PC20 in a dose-dependent fashion from 3.9 mg/mL after placebo to 13.3 mg/mL after pMDI 100 μg, 19.0 mg/mL after 200 μg, 32.6 mg/mL after 400 μg: and 35.1 mg/mL after 800 μg. The half-maximum response dose for pMDI (ED50) was 104 μg. Salbutamol Turbuhaler 50 μg increased the PC20 to 10.0 mg/mL and 100 μg to 12.6 mg/mL. Salbutamol pMDI 200 μg provided significantly greater protection to methacholine than pMDI 100 μg or Turbuhaler 100 μg and significantly less protection than pMDI 400 μg (P < 0.05). This study demonstrates that the relative protective dose potency of inhaled beta-agonists can be determined by comparing their effects on methacholine airway responsiveness. The estimated relative protective dose potency for salbutamol Turbuhaler in comparison with pMDI was 1.38 (95% CI 0.67 to 2.87) at 50 μg and was 0.96 (95% CI 0.56 to 1.64) at 100 μg.