The contribution of the swallowed fraction of an inhaled dose of salmeterol to it systemic effects

Salmeterol is approximately eight times as potent as salbutamol for systemi c effects, This may be because the drug is eight times more potent on recep tors or there may be differences in systemic bioavailability. The systemic effects of salbutamol are limited by its fairly high first-pass metabolism, but the oral bioavailability of salmeterol is unknown, The contribution of the swallowed fraction of an inhaled dose of salmeterol to its systemic ef fects were analysed in a randomized, double-blind, crossover study. Twelve healthy subjects were given inhaled salmeterol 400 mu g, inhaled sal meterol 400 mu g plus oral activated charcoal or inhaled placebo plus oral activated charcoal on three separate days. Cardiac frequency (fc), Q-T inte rval corrected for heart rate (QTc), plasma potassium and glucose concentra tions were measured for 4 h following the inhaled drug, Salmeterol with and without oral charcoal produced significant changes for all measures compared to placebo. The magnitude of effect following salmete rol alone was significantly greater than that following salmeterol plus cha rcoal for fC and glucose (mean (95% confidence interval) differences 8 (2-1 3) beats.min(-1), 0.59 (0.04, 1.13) mmol.L-1, respectively) and nonsignific antly greater for QTc interval and potassium concentration. The differences between salmeterol given with and without charcoal suggest that 28-36% of the systemic response to salmeterol administered from a mete red-dose inhaler are due to drug absorbed from the gastrointestinal tract, Thus, most of the systemic effects are due to the inhaled fraction of the d rug.