Relative therapeutic index between inhaled formoterol and salbutamol in asthma patients

Abstract

A double-blind, randomized crossover study in 28 asthmatic patients assessed the relative therapeutic index for inhaled formoterol and salbutamol. Pre-drug administration FEV1 (mean 2.08 1) was 49-93% of predicted and reversibility 16-82% after inhalation of salbutamol. Patients inhaled single doses of formoterol (Oxis®) (4.5,18 and 54 μg, delivered doses) via Turbuhaler, salbutamol (Ventolin®) (200 and 1800 μg) 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 describe 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 4.5-54 μg given via Turbuhaler and salbutamol 200-1800 μg given via pMDI was estimated to be 2.5 in favour of formoterol; this trend was not statistically significant. © 2002 Elsevier Science Ltd.