Salmeterol, a new long acting inhaled beta 2 adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients.

Abstract

Salmeterol is a new inhaled 2 adrenoceptor agonist, which has been shown in animal experiments to produce a more prolonged bronchodilator effect than currently available f2 adrenoceptor agonists. It was studied in eight adult asthmatic patients. Each patient received on separate test days salbutamol 200 pg and salmeterol 50, 100, and 200 pg according to a randomised, double blind, crossover design. FEV1, peak expiratory flow (PEF), heart rate, blood pressure, and tremor were recorded in the clinic for six hours after drug inhalation; PEF was recorded for a further six hours at home. All three doses ofsalmeterol produced peak increases in FEV1 (mean 0*5-048 1) and PEF (71-100 I/min) similar to those produced by salbutamol 200 yg (051 and 74 1/min). After salbutamol FEVy and PEF had returned to baseline within six hours, but after all three doses of salmeterol more than half of the maximum bronchodilator effect remained after 12 hours. The effects ofsalbutamol and the two lower doses ofsalmeterol (50 and 100 ug) on cardiovascular measurements and on tremor were similar, whereas after salmeterol 200 pg there was a small decrease in diastolic blood pressure and an increase in heart rate and tremor. Thus inhaled salmeterol has a long acting bronchodilator action in asthmatic patients. This effect may be of value in the treatment of asthma, particularly in patients with nocturnal symptoms.

Why are long-acting beta-adrenoceptor agonists long-acting?

“…This partitioning behaviour has been unequivocally demonstrated by the studies of RHOES and co-workers [19]. Using cholesterol and dioleoylphosphatidylcholine as artificial membrane lipid components reconstituted as uni-or multi-lamella liposomes, 3 H-labelled salmeterol was found to partition into the lipid extremely rapidly (<1 min) and completely (Kp (mem) 22,500, compared to salbutamol, Kp (mem) <4) but to diffuse from the lipid only slowly (half-life (T1/2) approximately 25 min at 25°). Salmeterol enters only the outer layer of uni-lamella liposomes and does not cross into underlying lipid layers of multi-lamella liposomes to any appreciable extent, implying that salmeterol maintains a highly specific orientation in the outermost leaf of the cell membrane [20].…”

“…Extensive clinical trial data have been obtained with these drugs, which indicate that they both cause significant bronchodilation for at least 12 h after a single administration [1][2][3][4][5]. Both compounds are well-tolerated and highly potent; the principal difference in their clinical pharmacology being the faster onset of action of formoterol compared to salmeterol [6][7][8].…”

Salmeterol, a novel, long‐acting β2‐adrenoceptor agonist: characterization of pharmacological activity in vitro and in vivo

“…Thus, the guinea-pig appears to resemble man, where again salmeterol is about ten fold more potent than salbutamol (Ullman & Svedmyr, 1988). Similarly, in terms of absolute duration of action, inhaled salbutamol has a well-established 4 to 6 h action in man (Leifer & Wittig, 1975), whereas preliminary data with salmeterol suggests a 12 h duration of action (Ullman & Svedmyr, 1988). On this basis, therefore, it appears that the conscious guinea-pig is of some predictive value, in terms of relative potencies and durations of action of inhaled 1i2-adrenoceptor bronchodilators in man.…”

Measurement of the Raman spectra and hygroscopicity of four pharmaceutical aerosols as they travel from pressurised metered dose inhalers (pMDI) to a model lung

“…Salbutamol (Ventalin™, Salamol™) has been a popular treatment for asthma 29 and COPD since 1968 (Icha, 2007), while Salmeterol (Serevent™) was introduced in 1988 as a longer 30 lasting alternative (Ullman & Svedmyr, 1988). 31…”