[Pharmacokinetics of theophylline and circadian rhythm]

In the purpose to evaluate the circadian changes of theophylline pharmacokinetic, 8 healthy subjects (age range 22-39 y, weight 54-91 kg) were given a single oral dose of 4,5 mg/kg theophylline solution. Administration was made randomly at 9 a.m. after 12 hours fasting and at 9 p.m. After evening administration the subjects remained awake during the night and a standardized meal was served 4 h and 9 h after theophylline intake. Plasma theophylline concentrations were measured by a high performance liquid chromatography. Absorption is significantly faster in the morning than in the evening but C max values were identical. Plasma elimination half-life is significantly different (8,01 +/- 1,95 h in the morning, 6,23 +/- 1,75 h in the evening). No significant modifications were observed of the area under the curve, the body clearance, the apparent volume of distribution. There were no differences in the total body clearance, the area under the concentration-time curve, the apparent volume of distribution.