Liu Ling, Wei Zhi-Wen, Jia Juan, Wang Yu-Jin
School of Forensic Medicine, Shanxi Medical University, Taiyuan 030001, China.
Fa Yi Xue Za Zhi. 2010 Oct;26(5):357-60.
To investigate the toxicokinetics profiles of ketamine and its main metabolite norketamine in rabbits.
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.
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.
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.
研究氯胺酮及其主要代谢产物去甲氯胺酮在兔体内的毒代动力学特征。
给兔口服0.15 g/kg氯胺酮盐酸盐。给药前及给药后不同时间点采集血清和尿液样本。采用气相色谱-氮磷检测器（GC-NPD）和气相色谱-质谱联用仪（GC-MS）测定氯胺酮和去甲氯胺酮的浓度。用WinNorLin程序模拟并计算房室模型和毒代动力学参数。实验过程中记录兔重要生命体征的变化。
氯胺酮和去甲氯胺酮的平均血清浓度-时间曲线符合一级动力学的二房室开放模型。氯胺酮和去甲氯胺酮的动力学方程分别为p(t)=121.760e(-0.0025t)+0.980e(-0.002t)+4.579e(-0.021t)和p(t)=640.919e(-0.03t)+1.023e(-0.001t)+9.784e(-0.031t)。氯胺酮在血清中的达峰时间和峰浓度分别为(40.950±12.098)min和(9.015±1.344)μg/mL。氯胺酮在兔体内的消除半衰期为(430.370±28.436)min。给药后30~240 min内，血清和尿液中氯胺酮浓度呈中等相关性。给兔口服氯胺酮后，兔在30 min出现中毒症状，120 min后消失。
氯胺酮和去甲氯胺酮在兔体内的毒代动力学参数及动力学方程可为法医鉴定合理采集标本及根据血清中氯胺酮浓度推断口服氯胺酮时间提供理论依据。
