COMPARISON OF THE RELATIVE AIRWAYS AND SYSTEMIC POTENCIES OF INHALED FENOTEROL AND SALBUTAMOL IN ASTHMATIC-PATIENTS

Background - There is controversy as to the relative safety of fenoter ol and salbutamol. No differences have been found in the relative card iac beta(1)/beta(2) receptor activity of inhaled fenoterol and salbuta mol in normal subjects. These initial findings have been extended by c omparing the respective potencies of equivalent doses by weight of fen oterol and salbutamol in asthmatic subjects, in terms of airways and s ystemic responses. Methods - Eighteen asthmatic patients of mean (SD) age 40 (14) years and a forced expiratory volume in one second (FEV(1) )% predicted of 56 (14)% (1.97 (0.66)1) were randomised to inhale feno terol (100 mu g/puff or 200 mu g/puff), salbutamol, or placebo (100 mu g/puff or 200 mu g/puff) on three separate days. Dose-response curves were constructed using cumulative doses of 100 mu g, 200 mu g, 400 mu g, 1000 mu g, 2000 mu g, and 4000 mu g, and airways and systemic resp onses were measured 20 minutes after each dose with 40 minute incremen ts. Dose ratios for the relative potency of fenoterol versus salbutamo l were calculated from the dose-response curves using regression analy sis of parallel slopes. Results - There was no difference in bronchodi lator potency between fenoterol and salbutamol (as median dose ratio): FEV(1) 1.1 (95% CI 0.4 to 4.6). In contrast, dose ratios for systemic responses showed that fenoterol was more potent than salbutamol: seru m potassium 3.7 (95% CI 2.0 to 6.0), tremor 5.7 (95% CI 1.4 to 10.2), heart rate 1.6 (95% CI 1.0 to 2.3). At a conventional dose of 200 mu g the only difference in response between the two drugs was observed fo r tremor (as mean difference): 0.23 log units (95% CI 0.06 to 0.41 log units). Conclusions - There was no difference in the bronchodilator p otency between fenoterol and salbutamol on a microgram equivalent basi s. In contrast, systemic potency was greater with fenoterol, although this difference was not clinically relevant at conventional dosages up to 200 mu g.