European Journal of Clinical Pharmacology

, Volume 32, Issue 3, pp 273–277 | Cite as

Kinetics of hexobarbital and dipyrone in critical care patients receiving high-dose pentobarbital

  • G. Heinemeyer
  • H. J. Gramm
  • W. Simgen
  • R. Dennhardt
  • I. Roots
Originals

Summary

The effect of pentobarbital treatment in a mean dose of 30 mg/kg/day on the clearance of hexobarbital (Evipan) and dipyrone (Novalgin) has been evaluated in critical care patients receiving a large number of drugs as comedication. Eleven patients treated with pentobarbital showed a hexobarbital half-life of 2.79 h and a total plasma clearance of 9.80 ml·min−1·kg−1 as compared to 10 patients without pentobarbital administration in whom there was a significantly longer half life (6.92 h) and lower clearance (2.97 ml·min−1·kg−1). The kinetics of hexobarbital were correlated with the urinary excretion of D-glucaric acid, a non-invasive parameter of drug metabolising activity. In 10 patients on pentobarbital, the total plasma clearance of N-4-methylaminoantipyrine, the active form of dipyrone, did not differ from that in 8 patients not receiving pentobarbital. As drug kinetics show great variability in these patients, it is difficult to discriminate enzyme induction from other mechanisms, for example competitive inhibition or changes in volume of distribution. In the presence of pentobarbital, however, induction of drug metabolising enzymes should be considered as a possible reason for the higher clearance of hexobarbital.

Key words

pentobarbital hexobarbital dipyrone intensive care D-glucaric acid pharmacokinetics drug interactions 

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Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • G. Heinemeyer
    • 1
  • H. J. Gramm
    • 2
  • W. Simgen
    • 3
  • R. Dennhardt
    • 2
  • I. Roots
    • 1
  1. 1.Institut für Klinische PharmakologieFreie Universität BerlinBerlinGermany
  2. 2.Klinik für Anästhesiologie und operative Intensivmedizin, Klinikum SteglitzFreie Universität BerlinBerlinGermany
  3. 3.Städtisches Krankenhaus MoabitBerlinGermany

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