Am. J. Respir. Crit. Care Med., Volume 160, Number 1, July 1999, 244-249

Comparison of the Relative Efficacy of Formoterol and Salmeterol in Asthmatic Patients

MONA PALMQVIST, THOMAS IBSEN, ANDERS MELLÉN, and JAN LÖTVALL

Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Heart and Lung Diseases, Göteborg University, Sahlgrenska University Hospital, Gothenburg, Sweden

Studies performed on airway smooth muscle in vitro have indicated that salmeterol is a partial agonist on the ₂-receptor in comparison to formoterol. In the present study we evaluated whether these pharmacological differences between salmeterol and formoterol also are applicable to asthmatic patients. The protective effects by increasing cumulative doses of formoterol (12, 60, 120 µg) and salmeterol (50, 250, 500 µg) on methacholine-induced bronchoconstriction were evaluated in a double-blind, crossover, placebo-controlled design. Patients were regularly treated with salbutamol 200 µg twice daily during the study period, to avoid variability in ₂-adrenoceptor tolerance. S-potassium, heart rate corrected Q-T interval (Q-T_c), and tremor score were followed as measures of systemic effects. Formoterol dose-dependently protected against methacholine responsiveness (4.6 doubling doses after 120 µg). Salmeterol, however, showed a flatter dose-response curve, and a significantly weaker maximal protective effect (2.8 doubling doses after 250 µg). Formoterol caused a significantly higher tremor score and a larger drop in S-potassium than salmeterol at the highest doses. These data show that salmeterol is a partial agonist on the ₂-receptor in relation to formoterol in human airways in vivo. Further studies are required to document the clinical consequences of this finding, for example in severe asthmatic patients.

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