European Journal of Clinical Pharmacology

, Volume 21, Issue 4, pp 343–350 | Cite as

Difference between single and multiple dose pharmacokinetics of orphenadrine hydrochloride in man

  • J. J. M. Labout
  • C. T. Thijssen
  • G. G. J. Keijser
  • W. Hespe


Plasma concentrations of orphenadrine were measured by a specific gaschromatographic method in 5 healthy male volunteers after a single oral dose of orphenadrine hydrochloride 100mg. The single dose pharmacokinetic profile of orphenadrine was evaluated from these data. The elimination half-life ranged from 13.2–20.1 h after the commercial tablet formulation. Plasma concentrations, determined in volunteers and patients under different conditions of repeated oral administration of the same formulation of orphenadrine hydrochloride exceeded the theoretical values, predicted from the single dose pharmacokinetics, by a factor 2 to 3. The elimination half-lives after discontinuation of treatment showed a 2 to 3-fold increase over the single dose values. This demonstrates a clear discrepancy between the multiple and single dose pharmacokinetics of orphenadrine. Experiments in dogs suggested competition for biotransformation between orphenadrine and its metabolite N-demethylorphenadrine. Product inhibition of this type could explain the observed discrepancy.

Key words

orphenadrine single dose multiple doses bioavailability pharmacokinetics N-demethylorphenadrine metabolism dog man 


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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • J. J. M. Labout
    • 1
  • C. T. Thijssen
    • 1
  • G. G. J. Keijser
    • 1
  • W. Hespe
    • 1
  1. 1.Gist-Brocades NV., Research and DevelopmentHaarlemThe Netherlands

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