title: [Toxicokinetics of ketamine in rabbits].
abstract: OBJECTIVE
  To investigate the toxicokinetics profiles of ketamine and its main metabolite norketamine in rabbits.
  
  
  METHODS
  The rabbits were administered orally the hydrochloride of ketamine with a dose of 0.15 g/kg. The serum and urine samples were collected before administration and at different time points after drug administration. The concentrations of ketamine and norketamine were determined by GC-NPD and GC-MS. Compartment model and toxicokinetics parameters were simulated and calculated by WinNorLin program. Changes of important vital signs of rabbits were recorded during the experiment.
  
  
  RESULTS
  The mean serum concentration-time profile of ketamine and norketamine were fitted to a two-compartment open model with first order kinetics. The kinetic equation of ketamine and norketamine were p(t) = 121.760 e(-0.0025t) +0.980 e(-0.002t) +4.579 e(-0.021 t) and p(t) = 640.919 e(-0.03 t) +1.023 e(-0.001 t) +9.784 e (-0.031 t), respectively. The peak time and the peak concentration of ketamine in serum were (40.950 +/- 12.098) min and (9.015 +/- 1.344) microg/mL, respectively. The elimination half-time of ketamine in rabbits was (430.370 +/- 28.436) min. The serum and urine showed a middle relation in concentrations of ketamine during 30-240 min after drug administration. After oral administration ketamine to rabbits, the toxic symptom on the rabbits occurred at 30 min and disappeared after 120 min.
  
  
  CONCLUSIONS
  The toxicokinetics parameters and kinetic equation of ketamine and norketamine in rabbits may provide the theoretical basis for forensic identification of reasonable specimen collection and inferring the time of oral administration ketamine from the ketamine concentration in serum.
authors.affiliation: School of Forensic Medicine, Shanxi Medical University, Taiyuan 030001, China. liulingoo@126.com
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Wei
authors.forename: Juan
authors.initials: J
authors.lastname: Jia
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000778:Anesthetics, Dissociative / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006339:Heart Rate / Q000187:drug effects; D007649:Ketamine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity* / Q000652:urine; D008297:Male; D010468:Perceptual Disorders / Q000209:etiology; D011817:Rabbits; D011897:Random Allocation; D013997:Time Factors
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine; C033419:norketamine