SYSTEMIC EFFECTS OF SALBUTAMOL AND SALMETEROL IN PATIENTS WITH ASTHMA

Background - Knowing the extent of the systemic effects of a new beta( 2) agonist relative to an established drug is important for the predic tion and interpretation of side effects. A recent study in which the e ffect of cumulative doses of salbutamol was compared with single doses of salmeterol suggested that, weight for weight, salmeterol may be up to 10 times more potent than salbutamol. This current study was desig ned to investigate further the dose equivalence of salmeterol and salb utamol. Methods - Twelve patients with mild asthma inhaled cumulative doses of placebo, salmeterol 25, 50, 100, and 200 mu g, and salbutamol 100, 500, 1000, and 1000 mu g on separate days at hourly intervals in a randomised double blind crossover study. Changes in forced expirato ry volume in one second (FEV(1)), heart rate, plasma potassium concent ration, systolic and diastolic blood pressure were measured. Dose equi valence was determined as the dose ratio of salmeterol to salbutamol f or the 50% maximum reponse to salbutamol. Results - No important chang es occurred in any measurements following placebo. Salmeterol and salb utamol caused a near maximum increase in FEV(1) following the first do se so the dose equivalence for the airway effects could not be estimat ed. Heart rate increased and plasma potassium concentration and diasto lic blood pressure decreased in a dose dependent manner following salm eterol and salbutamol, with median dose equivalences for salmeterol co mpared with salbutamol of 17.7, 7.8, and 7.6, respectively. Conclusion s - These results confirm that the systemic activity of salmeterol com pared with salbutamol is higher than would be expected from in vitro d ata, particularly for heart rate. Whether this is because of the relat ively high dose of salmeterol used or pharmacokinetic differences betw een the two drugs is uncertain.