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

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 α ) of 0.50 ± 0.07 h, elimination half-life ( t 1/2 β ) of 3.57 ± 0.55 h, area under the time concentration curve (AUC) of 1.03 ± 0.10 g/h l −1. The volume of distribution at steady state (Vd ss) 1.92 ± 0.22 l kg −1, volume of the central compartment of the two compartment pharmacokinetic model ( V c) 0.87 ± 0.09 l kg −1, and total body clearance (Cl T) of 0.60 ± 0.09 l/h kg −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 350 mg orphenadrine aspartate.