Zhu Yong-Liang, Li Shuang-Long, Chen Ke-Li, Ma Kun-Peng, Wu De-Qian, Qiu Xiang-Jun
Medical College of Henan University of Science and Technology, Luoyang 471023, People's Republic of China.
Drug Des Devel Ther. 2019 Sep 20;13:3343-3355. doi: 10.2147/DDDT.S221927. eCollection 2019.
To investigate the effects of Chinese herb Danzhi Xiaoyao pills on the pharmacokinetics of venlafaxine and its metabolites O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) in beagles by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
Six beagles (half male, half female) were chosen to test, being fasted before the experiment but having free access to drinking water 1 day before being fed drugs. After oral administration of venlafaxine hydrochloride tablets (10.28 mg/kg), the blood samples were collected in succession at different points in time. After 1-week washout period, Danzhi Xiaoyao pills (0.6g/kg) were given through oral administration to the six beagles every morning until the 7th day, venlafaxine hydrochloride tablets (10.28 mg/kg) were given after feeding Danzhi Xiaoyao pills (0.6g/kg) half an hour and blood samples were collected continuously at different points. All samples were analyzed by UPLC-MS/MS, and the main pharmacokinetic parameters of venlafaxine, ODV and NDV were computed by DAS 2.0.
The C of the venlafaxine group (control group) and the combination group (experimental group) were (2267.26±252.89) ng/mL and (1542.64±190.73) ng/mL, respectively. The AUC of the two groups were (13,934.79±3609.23) ng·h/mL and (8001.91±2167.58) ng·h/mL, respectively. The ODV C of the two groups were (2253.80±215.81) ng/mL and (2721.37±118.20) ng/mL, and AUC were (13,974.99±2784.04) ng·h/mL and (17,539.44±1894.29) ng·h/mL, respectively. The NDV C of the two groups were (50.98±5.76) ng/mL and (58.74±12.33) ng/mL, and AUC were (179.26±34.94) ng·h/mL and (220.68±51.41) ng·h/mL, respectively. After administration of Danzhi Xiaoyao pills, the C and AUC of venlafaxine decreased significantly, indicating that the plasma exposure of venlafaxine decreased. The increase of C and AUC of ODV and NDV indicated a rise in plasma exposure.
Danzhi Xiaoyao pills can accelerate the metabolism of venlafaxine in beagles. In clinical, when venlafaxine was co-administrated with Danzhi Xiaoyao pills, dose adjustment of venlafaxine should be taken into account.
采用超高效液相色谱-串联质谱法（UPLC-MS/MS）研究中药丹栀逍遥丸对比格犬体内文拉法辛及其代谢产物O-去甲基文拉法辛（ODV）和N-去甲基文拉法辛（NDV）药代动力学的影响。
选取6只比格犬（雌雄各半）进行试验，试验前禁食，给药前1天可自由饮水。口服盐酸文拉法辛片（10.28 mg/kg）后，于不同时间点连续采集血样。经过1周的洗脱期后，6只比格犬每天早晨口服丹栀逍遥丸（0.6g/kg），直至第7天，在服用丹栀逍遥丸（0.6g/kg）半小时后口服盐酸文拉法辛片（10.28 mg/kg），并于不同时间点连续采集血样。所有样品采用UPLC-MS/MS进行分析，通过DAS 2.0计算文拉法辛、ODV和NDV的主要药代动力学参数。
文拉法辛组（对照组）和联合用药组（试验组）的C分别为（2267.26±252.89）ng/mL和（1542.64±190.73）ng/mL。两组的AUC分别为（13934.79±3609.23）ng·h/mL和（8001.91±2167.58）ng·h/mL。两组的ODV C分别为（2253.80±215.81）ng/mL和（2721.37±118.20）ng/mL，AUC分别为（13974.99±2784.04）ng·h/mL和（17539.44±1894.29）ng·h/mL。两组的NDV C分别为（50.98±5.76）ng/mL和（58.74±12.33）ng/mL，AUC分别为（179.26±34.94）ng·h/mL和（220.68±51.41）ng·h/mL。服用丹栀逍遥丸后，文拉法辛的C和AUC显著降低，表明文拉法辛的血浆暴露量降低。ODV和NDV的C和AUC升高表明血浆暴露量增加。
丹栀逍遥丸可加速比格犬体内文拉法辛的代谢。临床上，当文拉法辛与丹栀逍遥丸合用时，应考虑调整文拉法辛的剂量。
