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 fenoterol and salbutamol. No differences have been found in the relative cardiac beta 1/beta 2 receptor activity of inhaled fenoterol and salbutamol in normal subjects. These initial findings have been extended by comparing the respective potencies of equivalent doses by weight of fenoterol and salbutamol in asthmatic subjects, in terms of airways and systemic responses.


METHODS
Eighteen asthmatic patients of mean (SD) age 40 (14) years and a forced expiratory volume in one second (FEV1)% predicted of 56 (14)% (1.97 (0.66)1) were randomised to inhale fenoterol (100 micrograms/puff or 200 micrograms/puff), salbutamol, or placebo (100 micrograms/puff or 200 micrograms/puff) on three separate days. Dose-response curves were constructed using cumulative doses of 100 micrograms, 200 micrograms, 400 micrograms, 1000 micrograms, 2000 micrograms, and 4000 micrograms, and airways and systemic responses were measured 20 minutes after each dose with 40 minute increments. Dose ratios for the relative potency of fenoterol versus salbutamol were calculated from the dose-response curves using regression analysis of parallel slopes.


RESULTS
There was no difference in bronchodilator potency between fenoterol and salbutamol (as median dose ratio): FEV1 1.1 (95% CI 0.4 to 4.6). In contrast, dose ratios for systemic responses showed that fenoterol was more potent than salbutamol: serum 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 micrograms the only difference in response between the two drugs was observed for 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 potency between fenoterol and salbutamol on a microgram equivalent basis. In contrast, systemic potency was greater with fenoterol, although this difference was not clinically relevant at conventional dosages up to 200 micrograms.
Lipworth
B J
BJ
Department of Clinical Pharmacology, University of Dundee, Ninewells Hospital and Medical School, UK.
Newnham
D M
DM
Clark
R A
RA
Dhillon
D P
DP
Winter
J H
JH
McDevitt
D G
DG
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy*; D001794:Blood Pressure; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D005280:Fenoterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D011188:Potassium / Q000378:metabolism; D014797:Vital Capacity
D005280:Fenoterol; D000420:Albuterol; D011188:Potassium