Systemic effects ofsalbutamol andsalmeterol in patients withasthma

Background - Knowingtheextentofthe systemic effects ofa new P2agonist relative toan established drugisimportant forthe prediction and interpretation of side effects. A recentstudyinwhichtheeffect ofcumulative dosesofsalbutamol was comparedwithsingle dosesofsalmeterol suggested that, weightforweight, salmeterol may beup to10timesmore potent thansalbutamol. Thiscurrentstudy was designed toinvestigate further thedose equivalence ofsalmeterol andsalbutamol. Methods- Twelvepatients withmild asthmainhaled cumulative dosesofplacebo,salmeterol 25,50,100,and200pg, andsalbutamol 100,500,1000, and1000pg on separatedaysathourlyintervals ina randomised doubleblind crossoverstudy. Changesinforcedexpiratory volumein one second(FEVy), heartrate,plasma potassiumconcentration, systolic and diastolic bloodpressure were measured. Doseequivalence was determined as the doseratio ofsalmeterol tosalbutamol for the50% maximum reponse to salbutamol. Results - Noimportant changes occurred inany measurementsfollowing placebo. Salmeterol andsalbutamol caused a near maximum increase inFEV,following the firstdoseso thedoseequivalence forthe airwayeffects couldnot be estimated. Heartrateincreased andplasmapotassiumconcentration and diastolic blood pressure decreased ina dosedependent manner following salmeterol andsalbutamol,withmediandoseequivalences for salmeterol comparedwithsalbutamol of 17-7, 7-8, and7-6, respectively. Conclusions - Theseresults confirm that thesystemic activity ofsalmeterol comparedwithsalbutamol ishigherthan wouldbe expected frominvitrodata, particularly forheartrate.Whetherthis isbecauseoftherelatively highdoseof salmeterolused or pharmacokinetic differences betweenthetwo drugsis uncertain.