PARTIAL VS FULL BETA-RECEPTOR AGONISM - A CLINICAL-STUDY OF INHALED ALBUTEROL AND FENOTEROL

Study objective: To compare the maximal extrapulmonary effects of the beta-agonists albuterol and fenoterol in eight healthy volunteers. Sub jects and methods: In this double-blind study, we have examined the ma ximum cardiac effects (electromechanical systole [QS(2)I]-a measure of inotropy, heart rate, BP) and metabolic effects (plasma K+ and cyclic adenosine monophosphate [cAMP]) of repeated inhalation of albuterol a nd fenoterol. In eight healthy volunteers, 400 mu g of each drug was a dministered every 10 min until QS(2)I and plasma K+ had reached a plat eau (+/-0.1 mmol/L for K+, and +/-10 ms for QS(2)I). The maximum respo nse (Emax) and the dose of albuterol required to produce 50% of the ma ximum response to fenoterol (ED(50F)) were calculated. Results: The Em ax for fenoterol was significantly greater than albuterol for plasma K + (-1.4 vs -1.03 mmol/L; p<0.002), QS(2)I (-71.8 vs -57.5 ms; p=0.047) , and cAMP (33.8 vs 18.1 nmol/L; p<0.002). The dose required to produc e the ED(50F) was significantly greater for albuterol than for fenoter ol with potency ratios of 1.75, 1.61, and 2.26 for plasma K+, QS(2)I, and cAMP, respectively. There were no significant differences between fenoterol and albuterol with respect to heart rate (Emax, 44.9 vs 32.5 beats/min; p=0.19; potency ratio, 1.98; p=0.052). Conclusions: These findings suggest that albuterol behaves as a partial agonist at beta-r eceptors when compared with fenoterol, and that when inhaled in doses currently recommended for severe asthma, albuterol will result in less er maximum cardiac and metabolic effects than fenoterol. These finding s are consistent with the hypothesis that the property of full recepto r agonism may contribute to the increased risk of death associated wit h fenoterol.