ISSN:
1432-1041
Keywords:
orphenadrine
;
single dose
;
multiple doses
;
bioavailability
;
pharmacokinetics
;
N-demethylorphenadrine
;
metabolism
;
dog
;
man
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00637624
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