Circadian time-dependent kinetics of theophylline and its modulation by phenobarbital pretreatment in rats

D. Zeruesenay, W. Siegmund, G. Franke, M. Zschiesche

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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 19:000 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). Key Words: Theophylline - Chronopharmacokinetics - Phenobarbital - Enzyme induction.

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalChronobiology International
Issue number2
StatePublished - Jan 1 1993


ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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