氯胺酮对家兔依非韦伦药代动力学的影响

目的在新西兰家兔中,研究麻醉药氯胺酮（KTM）对抗艾滋病药依非韦伦（EFV）药代动力学的影响。方法选择新西兰家兔12只,随机分为两组,均予EFV 2mL/kg灌胃,实验组在给予EFV后5分钟静脉注射KTM 10mg/kg,对照组静脉注射同等容量的生理盐水,分别于灌胃前和即刻,以及给药0.25、0.5、1、2、3、4、6、8、10、12、14、24小时后,自兔耳中央动脉取血0.3mL,用液相色谱串联质谱法（LC-MS/MS）测定血浆中EFV的浓度,进行药物动力学参数的计算与比较。结果两组新西兰家兔的EFV药代动力学过程均符合二室模型。对照组和试验组的最高血药浓度（Cmax）分别为（2.1±1.21）mg和（3.6±1.37）mg./L-1（P〈0.05）,消除给药剂量的63.2%所需要的时间（MRT）分别为（8.4±4.08）hr和（10.1±2.70）hr（P〈0.05）,药时曲线下面积（AUC）分别为（17.1±9.17）mg和（39.1±14.95）mg./L-1.hr-1（P〈0.05）。结论 EFV治疗后应用KTM麻醉可能升高EFV的血药浓度。

Effect of ketamine on pharmacokinetics of efavirenz in rabbits

Objective To study the effect of ketamine on pharmacokinetic changes of efavirenz（EFV） in rabbits.Methods Twelve rabbits were randomly allocated into two groups.All rabbits were given EFV 2mL/kg by gavage.Five minutes later the rabbits in the test group were injected 10mg/kg ketamine intravenously while those in the control group were injected equal volume of saline intravenously.Arterial blood samples were taken before and immediately after gavage,and in 0.25,0.5,1,2,3,4,6,8,10,12,14 and 24 hrs after ketamine administration.The plasma EFV concentrations were determined with liquid chromatographic-tandem mass spectrometric（LC-MS/MS）.Results The pharmacokinetic change of EFV conformed to two compartment model.The maximum concentrations（Cmax）in the control and test groups were（2.1±1.21）mg and（3.6±1.37） mg·/L-1,respectively（P0.05）,the maximum required time（MRT） was（8.4±4.08） hr.and（10.1±2.70） hr.,respectively（P0.05）,and the area under curves（AUC） was（17.1±9.17）mg and（39.1±14.95） mg·/ L-1·hr-1,respectively,（P0.05）.Conclusion Ketamine could elevate EFV concentrations in rabbits.