CIRCADIAN TIME-DEPENDENT KINETICS OF THEOPHYLLINE AND ITS MODULATION BY PHENOBARBITAL PRETREATMENT IN RATS

The pharmacokinetics of theophylline (TPH, 10 mg/kg i.v.) were assessed in rats (natural light-dark span, June 9-10) after i.p. pretreatment with saline and 80 mg/kg phenobarbital (PB), respectively, for 3 consecutive days at either 07:00 h or at 19:00 h. Serum concentrations of TPH were assayed by high-performance liquid chromatography. No significant differences of the elimination rates of TPH could be found between the times of TPH administration (clearance: 1.17 +/- 0.17 ml/kg/min at 07:00 h vs. 1.23 +/- 0.17 ml/kg/min at 19:00 hours). PB premedication markedly accelerated TPH elimination. The increase in clearance values was more expressed when TPH was injected at 07:00 h than at 19:00 h (2.48 +/- 0.67 vs. 2.06 +/- 0.41 ml/kg/min, p < 0.01).