European Journal of Clinical Pharmacology

, Volume 26, Issue 4, pp 499–503 | Cite as

Single and multiple dose kinetics of clobazam, and clinical effects during multiple dosage

  • H. R. Ochs
  • D. J. Greenblatt
  • M. Lüttkenhorst
  • B. Verburg-Ochs


Sixteen healthy volunteers, aged 19 to 62 years, took a single 20-mg oral dose of clobazam and the serum concentrations of clobazam and desmethylclobazam were measured for the following 7 days. The mean kinetic variables for clobazam were: volume of distribution 1.31/kg, elimination half-life 24 h, total clearance 0.47 ml/min/kg. 13 of the volunteers then took clobazam 5 mg twice daily for 22 consecutive days. Serum concentrations were measured during and after this period. Both clobazam and desmethylclobazam showed slow and extensive accumulation, their steady-state kinetics being entirely consistent with those observed after single doses. Elimination of both compounds after termination of treatment was equally slow. Clinical self-rating of morning sedation indicated a significant increase over baseline in subjective perception of sedation during the treatment period, and this effect persisted into the washout period. However, sedation did not increase in parallel with accumulating levels of clobazam and desmethylclobazam, probably due to functional adaptation or tolerance.

Key words

benzodiazepines clobazam desmethylclobazam pharmacokinetics sedation accumulation 


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Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • H. R. Ochs
    • 1
    • 2
  • D. J. Greenblatt
    • 1
    • 2
  • M. Lüttkenhorst
    • 1
    • 2
  • B. Verburg-Ochs
    • 1
    • 2
  1. 1.Medizinische UniversitätsklinikBonnFederal Republic of Germany
  2. 2.the Division of Clinical PharmacologyTufts-New England Medical CenterBostonUSA

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