TIME AND THEOPHYLLINE CONCENTRATION HELP EXPLAIN THE RECOVERY OF PEAK FLOW FOLLOWING ACUTE AIRWAYS OBSTRUCTION - POPULATION ANALYSIS OF A RANDOMIZED CONCENTRATION CONTROLLED TRIAL

Peak expiratory flow rate, adverse effects and serum theophylline concentration were measured during treatment of episodes of severe airways obstruction. 174 patients were randomised to target theophylline concentrations of 10 mg/L or 20 mg/L The recovery of peak flow rate towards normal values was explicable in terms of time and theophylline concentration using semiparametric and parametric nonlinear regression models. In the absence of theophylline, recovery takes place with a half-time of 16 hours. Theophylline is less effective in achieving recovery than the passage of time but achieves 50% of possible recovery at a concentration of 11 mg/L. The action of theophylline is most marked at the start of treatment. It may no longer have important beneficial effects after 72 hours. The incidence of adverse effects increased at theophylline concentrations >20 mg/L.