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

Plasma concentrations of orphenadrine were measured by a specific gas chromatographic 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 ran...

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Bibliographic Details
Published inEuropean journal of clinical pharmacology Vol. 21; no. 4; p. 343
Main Authors Labout, J J, Thijssen, C t, Keijser, G G, Hespe, W
Format Journal Article
LanguageEnglish
Published Germany 01.01.1982
Subjects
Administration, Oral
Adult
Animals
Biotransformation
Chromatography, Gas
Dogs
Drug Administration Schedule
Half-Life
Humans
Kinetics
Male
Orphenadrine - administration & dosage
Orphenadrine - blood
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Summary:Plasma concentrations of orphenadrine were measured by a specific gas chromatographic 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 13.2-20.1h 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.
ISSN:0031-6970
DOI:10.1007/BF00637624