Time and Theophylline Concentration Help Explain the Recovery of Peak Flow Following Acute Airways Obstruction

SummaryPeak 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.

[1]  M. Chandler,et al.  Pulmonary Function in the Elderly: Response to Theophylline Bronchodilation , 1990, Journal of clinical pharmacology.

[2]  F. Follath,et al.  Theophylline serum concentration and therapeutic effect in severe acute bronchial obstruction: the optimal use of intravenously administered aminophylline. , 1982, American Review of Respiratory Disease.

[3]  L. Sheiner,et al.  Understanding the Dose-Effect Relationship , 1981, Clinical pharmacokinetics.

[4]  M. Aubier,et al.  A randomized, controlled trial of theophylline in patients with severe chronic obstructive pulmonary disease. , 1989, The New England journal of medicine.

[5]  D. Bates,et al.  Nonlinear mixed effects models for repeated measures data. , 1990, Biometrics.

[6]  R. Ogilvie,et al.  Rational intravenous doses of theophylline. , 1973, The New England journal of medicine.

[7]  R Couch,et al.  Theophylline Target Concentration in Severe Airways Obstruction — 10 or 20 mg/L? , 1993, Clinical pharmacokinetics.

[8]  Carl de Boor,et al.  A Practical Guide to Splines , 1978, Applied Mathematical Sciences.

[9]  A. Gelb,et al.  Aminophylline increases the toxicity but not the efficacy of an inhaled beta-adrenergic agonist in the treatment of acute exacerbations of asthma. , 1985, The American review of respiratory disease.

[10]  L. Benet,et al.  PREDNISOLONE PHARMACODYNAMICS ASSESSED BY INHIBITION OF THE MIXED LYMPHOCYTE REACTION , 1982, Transplantation.

[11]  W. Cleveland Robust Locally Weighted Regression and Smoothing Scatterplots , 1979 .