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.
Conclusion: 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.
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