Relative therapeutic index between inhaled formoterol and salbutamol in asthma patients

A double-blind, randomized crossover study in 28 asthmatic patients assessed the relative therapeutic in- dex for inhaled formoterol and salbutamol. Pre-drug administration FEV1 (mean 2.08 l) was 49--93% of predicted and reversibility16 --82% after inhalation of salbutamol. Patients inhaled single doses of formoterol (Oxis s ) (4.5,18 and 54mg, delivered doses) viaTurbuhaler, salbutamol (Ventolin s )( 200 and 1800mg) via pressurized metered dose inhaler (pMDI) and placebo at intervals of 48 h or more. Individual maximum FEV1 and minimum S-K + were calculated. Relative local (maximum FEV1) and systemic (minimum S-K + ) dose potencies, and their ratio, the relative therapeutic index, were estimated using a non-linear mixed effect model.The drug effects were well tolerated and dose dependent. A log-linear approximation was used to describe the bronchodilatory effect, whereas a sigmoid approximation was more apt to de- scribe the decrease in serum potassium concentration. A bivariate dose--response model based on these principles was fitted simultaneously to all data.The mean relative therapeutic index between formoterol 4.5--54mg given viaTurbuhaler and salbutamol 200 --1800mg given via pMDI was estimated to be 2.5 in favour of formoterol; this trend was not statisti- cally significant.r 2002 Elsevier Science Ltd