Apparent decrease in population clearance of theophylline: Implications for dosage

Background: Having observed in recent years that the theophylline dose requirements needed to attain peak serum concentrations of 10 to 20 mu g/ml infrequently reached previously described mean values, we hypothesized that a downward shift in the range of dose requirements had occurred among patients with asthma. Study design: We examined dosage requirements needed to attain peak serum concentrations of 10 to 20 mu g/ml in all patients with chronic asthma treated with theophylline by the Pediatric Allergy and Pulmonary Clinic at the University of Iowa from 1990 to 1994 (n = 300) and at the Pediatric Pulmonary Clinic at the University of Florida from 1992 to 1995 (n = 93), We then compared these doses to previous dose requirements from 1978 to 1983 determined in the same manner. Results: Despite similar mean peak serum concentrations during both time periods (14 mu g/ml), mean theophylline dosage requirements during the period of this study were approximately 25% lower among all age groups than those previously observed (p < 0.001), There were no significant differences in mean dosage requirements between the Iowa and Florida patients in any age group examined. Conclusions: Theophylline dose requirements needed to attain serum concentrations of 10 to 20 mu g/ml have decreased significantly from those on which current dosing recommendations are based, This suggests a decrease in mean clearance of the population.