Inhalation of beta-stimulants: Dose-response relationship

Abstract

An attempt was made to assess the dose-response (D-R) relationship of a beta-agonist (salbutamol) in 14 patients with bronchial asthma by inhalation of a wet aerosol. The patients were divided into two equal groups. Sequences of inhalations were administered with increasing doses at timed intervals, such that a cumulation of the individual doses could be assumed. In a first trial the cumulative doses given at intervals of 30 minutes amounted to 40, 200, 1000 and 5000 µg salbutamol, respectively. The graded responses were assessed by measuring the specific airway conductance (SGaw). With this procedure, consistent mean D-R curves could be established in both patient groups in spite of considerable individual variations. In a second trial the same sequences of inhalations but with a lower overall dose of 1000 µg of salbutamol were given to the patients of one group; the final response was equivalent to that predicted from their mean D-R curve. Hence, the conclusion seems justified that D-R curves determined by cumulative inhalations are real and that they are not the result of a sequential stimulation of spatially different beta-receptors due to a sequentially improved penetration and deposition of the aerosol within the bronchial tree. The calculated median effective dose (ED₅₀) of salbutamol for all 14 patients amounted to 110 µg. According to the D-R curve 1250 µg of salbutamol (equivalent to 5 drops of the 0.5% Ventolin® solution) dissolved in 2 ml of saline appears to be an appropriate dose which yields a response of 85% of the maximum without detectable side effects.