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

Res Vet Sci. 2008 Dec;85(3):563-9. doi: 10.1016/j.rvsc.2008.01.006. Epub 2008 Mar 5.

Abstract

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.

MeSH terms

  • Animals
  • Area Under Curve
  • Camelus / metabolism*
  • Chromatography, Ion Exchange
  • Gas Chromatography-Mass Spectrometry
  • Half-Life
  • Injections, Intravenous
  • Kinetics
  • Male
  • Muscle Relaxants, Central / administration & dosage
  • Muscle Relaxants, Central / blood
  • Muscle Relaxants, Central / pharmacokinetics
  • Muscle Relaxants, Central / urine
  • Orphenadrine / administration & dosage
  • Orphenadrine / blood*
  • Orphenadrine / pharmacokinetics*
  • Orphenadrine / urine

Substances

  • Muscle Relaxants, Central
  • Orphenadrine