THE THERAPEUTIC range of plasma concentrations of the antiasthmatic drug theophylline is relatively narrow (approximately 10 to 20μg/ml). It is difficult to design safe and effective dosage regimens for this drug without monitoring plasma concentrations because of the pronounced interindividual differences in the body clearance of theophylline. These differences are magnified by the effects of disease, particularly congestive heart failure and impaired liver function, which have been found to be associated with a very low theophylline body clearance.
Adverse effects of theophylline occur at high plasma concentrations of this drug. Zwillich and co-workers1 described eight patients in whom grand mal seizures developed during intravenous theophylline therapy, and of whom four died. The average serum theophylline concentration in these patients was 53±4.8μg/ml. A group of patients with less severe adverse effects had an average serum theophylline concentration of 35±1.8μg/ml, while patients without apparent adverse effects had an average serum concentration