Circadian changes in the absorption and elimination of theophylline in patients with bronchial obstruction

Circadian variation in the serum concentration of theophylline has been reported in most patients receiving slow release oral preparations. To examine further the mechanism and clinical relevance of this change, an investigation has been made into the diurnal fluctuation in elimination kinetics during i.v. administration of theophylline and its serum concentration profile on oral treatment with a slow release preparation, in 8 hospitalized patients receiving it for bronchial obstruction. After reaching steady-state on a constant intravenous infusion, the total body clearance of theophylline (CL) was determined every 4-6 h from the steady-state concentration and the infusion rate. No systematic trend indicative of circadian changes in elimination kinetics was observed. The intraindividual fluctuation in CL during the observation period was small (coefficient of variation 4-11%). In contrast, on oral dosing a smaller area under the serum concentration-time curve was found during the night time (22.00-06.00). The results show that the circadian variation described in serum theophylline concentrations is due to delayed absorption at night. The elimination kinetics of theophylline do not change.