Temporal variations in trough serum theophylline concentrations at steady state.

Temporal variations in serum theophylline concentrations were observed in 14 healthy volunteers receiving multiple doses of theophylline. After repeated oral doses (6.9--18.2 mg/kg/day) of theophylline as either a nonalcoholic aminophylline solution or a controlled-release capsule, trough theophylline levels at steady state were significantly higher (p less than 0.05) in the morning than in the afternoon or evening. With the solution, the mean (+/-SE) trough serum level at 7 am was 11.1 +/- 0.9 micrograms/ml, and at 1 pm it was 9.6 +/- 0.8 micrograms/ml. With the capsule, the mean (+/-SE) trough serum level at 8 am was 13.8 +/- 0.9 micrograms/ml, and at 8 pm it was 10.7 +/- 0.9 micrograms/ml. Temporal variations in serum theophylline concentrations have not been reported previously and may be important in therapeutic monitoring.