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.
Elghazali
M
M
Camel Racing Forensic Laboratory, Directorate for Forensic Sciences, Abu Dhabi, United Arab Emirates. mezali@yahoo.com
Wasfi
I A
IA
Abdel Hadi
A A
AA
Latum
A M
AM
D000818:Animals; D019540:Area Under Curve; D002162:Camelus / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D009966:Orphenadrine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics* / Q000652:urine
D009125:Muscle Relaxants, Central; D009966:Orphenadrine