AN OVERVIEW OF 9 CLINICAL-TRIALS OF SALMETEROL IN AN ASTHMATIC POPULATION

In an attempt to establish the protection afforded by regular salmeter ol use against induced bronchoconstriction in asthmatic patients, a me ta-anaiysis was conducted on nine double-blind clinical trials that fu lfilled the inclusion criteria. In each trial, subjects were randomly assigned to receive either salmeterol 50 mu g twice daily or a compara tor (placebo or salbutamol). Two hundred and twenty-five asthmatic sub jects had at least one PC20 or PD20 (histamine or methacholine concent ration or dose producing 20% fall in forced expiratory volume in 1 s) measurement recorded within 1 h to 16 weeks after the first dose, and up to 31 days after the last dose, of medication. One hour after the f irst dose of salmeterol, there was a 3.5-fold increase in doubling dos e compared to baseline. Within 12 h of the first dose, the level of pr otection was 1.5 doubling doses, and protection was maintained at 0.5- 1.5 doubling doses over 16 weeks' treatment. This level of protection was maintained for up to 60 h after the last dose. At no time during t he washout period did the level of protection fall below zero. Salmete rol afforded significantly greater protection at all time points durin g the treatment period than comparator agents, but there was no signif icant difference during the washout period. In conclusion, salmeterol affords protection against bronchoconstrictor stimuli, and any reducti on in this bronchoprotective effect occurred during the first few days of treatment. During long-term salmeterol treatment, there was mainta ined significant protection that showed no evidence of attenuation aft er 16 weeks' treatment. Furthermore, there was no evidence of rebound deterioration in bronchial responsiveness after cessation of salmetero l treatment.