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 m u g/ml infrequently reached previously described mean values, we hypot hesized that a downward shift in the range of dose requirements had oc curred among patients with asthma. Study design: We examined dosage re quirements needed to attain peak serum concentrations of 10 to 20 mu g /ml in all patients with chronic asthma treated with theophylline by t he Pediatric Allergy and Pulmonary Clinic at the University of Iowa fr om 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 th ese doses to previous dose requirements from 1978 to 1983 determined i n the same manner. Results: Despite similar mean peak serum concentrat ions during both time periods (14 mu g/ml), mean theophylline dosage r equirements during the period of this study were approximately 25% low er among all age groups than those previously observed (p < 0.001), Th ere were no significant differences in mean dosage requirements betwee n 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.