【作者】 胡礼军； 江晓佳； 卢浩扬； 王占璋； 倪晓佳； 尚德为； 林朝仙； 温预关；

【Author】 HU Li-jun;JIANG Xiao-jia;LU Hao-yang;WANG Zhan-zhang;SHANG De-wei;LIN Chao-xian;WEN Yu-guan;The First Affiliated Hospital of Shantou University Medical College;The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital);Jinan University;

【机构】 汕头大学医学院第一附属医院； 广州医科大学附属脑科医院(广州市惠爱医院)； 暨南大学；

【摘要】 目的:比较文拉法辛及其代谢物在健康大鼠和抑郁大鼠的药代动力学差异。方法:8只健康大鼠和8只抑郁大鼠分别灌胃盐酸文拉法辛原料药(20.25mg·kg^-1)。采用经验证的液相色谱-串联质谱法（LC-MS/MS）测定血浆中文拉法辛及其活性代谢产物O-去甲基文拉法辛的浓度,经DAS 3.2.4软件计算药动学参数。结果:血浆样品经蛋白沉淀,在选定的色谱质谱条件下文拉法辛、O-去甲基文拉法辛与内标及血浆杂质分离良好,文拉法辛、O-去甲基文拉法辛分别在4⁴00 ng·mL^-1内线性良好,相对回收率在92.44¹03.86%,日内和日间RSD均小于10.57%。健康和抑郁大鼠血浆中文拉法辛的T_max、C_max、t_1/2、AUC_0-8和MRT0-8分别为（0.28±0.18）h和（0.38±0.14）h、（382.62±352.34）μg·L^-1和（487.28±267.18）μg·L^-1、（1.51±1.26）h和（2.10±0.97）h、（339.37±175.69）μg·L^-1·h^-1和（703.25±334.22）μg·L^-1·h^-1、（1.64±0.55）h和（1.96±0.86）h;O-去甲基文拉法辛的T_max、C_max、t_1/2、AUC_0-8和MRT0-8分别为（0.75±0.93）h和（0.30±0.02）h、（39.33±27.34）μg·L^-1和（101.61±68.13）μg·L^-1、（2.30±0.91）h和（3.52±1.78）h、（80.88±46.91）μg·L^-1·h^-1和（180.93±105.00）μg·L^-1·h^-1、（2.37±0.88）h和（2.47±0.75）h。结论:抑郁大鼠体内文拉法辛及O-去甲基文拉法辛药时曲线下面积(AUC_0-8)、半衰期t_1/2和达峰浓度C_max均大于健康大鼠,表明健康大鼠与抑郁大鼠对文拉法辛有不同的药动学过程。更多还原

【Abstract】 OBJECTIVE To compare the pharmacokinetics differences of venlafaxine and its metabolites in healthy and depression rats. METHODS Eight healthy and eight depression rats were treated with a single venlafaxine hydrochloride at a dosage of 20.25 mg·kg^-1 by gavage. The plasma concentrations of venlafaxine and O-desmethyl venlafaxine were determined by a validated liquid chromatography-tandem mass spectrometry（LC-MS/MS） method, and the pharmacokinetic parameters of the two material were analyzed using DAS 3.2.4 software. RESULTS Blood samples were deproteinized. The calibration curves of venlafaxine and O-desmethyl venlafaxine were linear in the range from 4 to 400 ng·mL^-1. The relative recovery was 92.44¹03.86 %. The intra-day and inter-day RSDs were less than 10.57 %. The main pharmaeokinetic parameters of venlafaxine in healthy and depression rats were as follows:T_max:（0.28±0.18） and（0.38±0.14） h; C_max:（382.62±352.34） and（487.28±267.18） μg·L^-1; t_1/2:（1.51±1.26） and（2.10±0.97） h; AUC_0-8:（339.37±175.69） and（703.25±334.22） μg·L^-1·h^-1; MRT0-8:（1.64±0.55） and（1.96±0.86） h. The main pharmaeokinetic parameters of O-desmethyl venlafaxine in healthy and depression rats were as follows:T_max:（0.75±0.93） and（0.30±0.02） h; C_max:（39.33±27.34） and（101.61±68.13） μg·L^-1; t_1/2:（2.30±0.92） and（3.52±1.78） h; AUC_0-8:（80.88±46.92） and（180.93±105.00） μg·L^-1·h^-1; MRT0-8:（2.37±0.88） and（2.47±0.75） h.CONCLUSION The area under the curve(AUC_0-8), the half-life t_1/2 and the peak concentration C_max of venlafaxine and O-desmethyl venlafaxine in the depressed rats were all higher than those in the healthy rats, indicating that there have different pharmacokinetic processes for venlafaxine in depression and healthy rats.更多还原