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Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients

European Journal of Drug Metabolism and Pharmacokinetics volume 23, pages 255–258 (1998)Cite this article

Summary

The pharmacokinetics of midazolam and of its main metabolite, 1-hydroxymidazolam, were investigated in intensive care patients after intravenous bolus of 0.2mg/kg followed by a 0.1mg/kg/h intravenous infusion of midazolam over 2 hours. A wide interpatient variability of the main pharmacokinetic parameters of midazolam was found. The mean values of elimination half life and volume of distribution, 4.5±5.4 h and 1.7±0.7l/kg respectively, were higher than those reported in healthy subjects. Total plasma clearance was significantly increased in patients taking drugs that induce hepatic metabolism. Significant concentrations of the unconjugated form of 1-hydroxymidazolam were recovered in plasma. The volume of distribution and the elimination half life of the metabolite were higher than those of the parent drug. These results show that 1-hydroxymidazolam might contribute to the pharmacodynamic effect of midazolam and consequently must be taken into account during pharmacokinetic and pharmacodynamic studies.

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Affiliations

  1. Département de Pharmacie Clinique, de Pharmacocinétique et d' Evaluation du Médicament, Institut des Sciences Pharmaceutiques et Biologiques, 8 avenue Rockefeller, 69373, Lyon Cedex 08, France

    R. Boulieu & B. Lehmann

  2. Service Pharmaceutique, Hôpital Neuro-Cardiologique, Lyon, France

    R. Boulieu & B. Lehmann

  3. Département d' Anesthésie-Réanimation, Hôpital Neuro-Cardiologique, Lyon, France

    F. Salord

  4. Laboratoire d' Electroencéphalographie, Hôpital Neuro-Cardiologique, Lyon, France

    C. Fisher

  5. INSERM U 280, Lyon, France

    D. Morlet

Authors
  1. R. Boulieu
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  2. B. Lehmann
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  3. F. Salord
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  4. C. Fisher
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  5. D. Morlet
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Boulieu, R., Lehmann, B., Salord, F. et al. Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients. European Journal of Drug Metabolism and Pharmacokinetics 23, 255–258 (1998). https://doi.org/10.1007/BF03189348

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  • DOI: https://doi.org/10.1007/BF03189348

Keywords

  • Midazolam
  • 1-hydroxymidazolam
  • pharmacokinetics
  • intensive care patients