ABSTRACT
The bioavailability of orphenadrine hydrochloride after a single intramuscular injection was compared to that after a single oral dose by following serial plasma concentration estimations of the unchanged drug. Eight subjects received 40 mg orphenadrine HCl intramuscularly and 50 mg orally on separate occasions 1 week apart. The bioavailability of orphenadrine from the intramuscular dosage form proved to be equal to or even greater than that from the tablet. The first hour plasma concentrations after intramuscular doses were significantly higher than those after oral doses, supporting the clinical use of the intramuscular route in those indications where rapid effects of the drug are required.
Subject(s)
Orphenadrine/blood , Administration, Oral , Adult , Biological Availability , Female , Half-Life , Humans , Injections, Intramuscular , Male , Orphenadrine/administration & dosageABSTRACT
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.
Subject(s)
Orphenadrine/blood , Administration, Oral , Adult , Animals , Biotransformation , Chromatography, Gas , Dogs , Drug Administration Schedule , Half-Life , Humans , Kinetics , Male , Orphenadrine/administration & dosageABSTRACT
A gas chromatographic and extraction method for the assay of orphenadrine in plasma and urine has been developed, in which diphenhydramine is used as the internal standard. The procedure involves extraction with isopentane and alkali flame ionization (nitrogen) detection. Orphenadrine N-oxide and N-dealkylated orphenadrine did not interfere with the analysis. Orphenadrine concentrations down to 1 ng/ml can be determined. Application in a pharmacokinetic/bioavailability study is reported.
