Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration.

The pharmacokinetics of orphenadrine (ORPH) following a single intravenous (i.v.) dose was investigated in six camels (Camelus dormedarius). Orphenadrine was extracted from the plasma using a simple sensitive liquid-liquid extraction method and determined by gas chromatography/mass spectrometry (GC/MS). Following i.v. administration plasma concentrations of ORPH decline bi-exponentially with distribution half-life (t(1/2)(alpha)) of 0.50+/-0.07h, elimination half-life (t(1/2)(beta)) of 3.57+/-0.55h, area under the time concentration curve (AUC) of 1.03+/-0.10g/hl(-1). The volume of distribution at steady state (Vd(ss)) 1.92+/-0.22lkg(-1), volume of the central compartment of the two compartment pharmacokinetic model (V(c)) 0.87+/-0.09lkg(-1), and total body clearance (Cl(T)) of 0.60+/-0.09l/hkg(-1). Three orphenadrine metabolites were identified in urine samples of camels. The first metabolite N-desmethyl-orphenadrine resulted from N-dealkylation of ORPH with molecular ion m/z 255. The second N,N-didesmethyl-orphenadrine, resulted from N-didesmethylation with molecular ion m/z 241. The third metabolite, hydroxyl-orphenadrine, resulted from the hydroxylation of ORPH with molecular ion m/z 285. ORPH and its metabolites in camel were extensively eliminated in conjugated form. ORPH remains detectable in camel urine for three days after i.v. administration of a single dose of 350mg orphenadrine aspartate.

Acute intoxication with orphenadrine and clozapine.

This report describes a fatal intoxication with two different drugs: clozapine and orphenadrine. A 38-year-old man was found dead in the bedroom of his residence. Near the body were found various empty pharmaceutical boxes, employed in schizophrenic therapy, two of them containing clozapine and orphenadrine. High concentrations of clozapine and orphenadrine detected in blood, urine and gastric content were related to death. These compounds were identified and quantitated by liquid-liquid extraction followed by gas chromatographic/mass spectrometry (GC/MS) analysis.

A report on the analysis of orphenadrine in post mortem specimens.

A discussion of the methods reported for the analysis of orphenadrine is given. The drug levels in biological specimens and the methods reported vary widely. The stability and extractability of orphenadrine is investigated and a method suggested, which uses subtilisin digestion of tissue followed by extraction with 1-chlorobutane. Body fluids are extracted directly by 1-chlorobutane after pH adjustment. Analysis is performed by gas chromatography with a nitrogen selective detector and no interferences are observed from bland specimens. The following levels are results from a case of a 19-year-old male who was found dead 2.5 hours after last being seen alive. This laboratory analysed the case using diphenhydramine as an internal standard: blood 18.1 micrograms/mL, liver 242 micrograms/g, urine 7.0 micrograms/mL, stomach contents 1452 mg.

Sensitive and specific gas chromatographic and extraction method for the determination of orphenadrine in human body fluids.

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.