辣椒素对文拉法辛药动学影响研究

The effects of capsaicin on pharmacokinetics of venlafaxine

目的:考察辣椒素对文拉法辛及其活性代谢物O-去甲基文拉法辛体内药动学的影响。方法:选取10只健康SD大鼠,采用自身对照方法,考察单剂量给予盐酸文拉法辛(20.25 mg·kg-1)(对照组)以及连续7 d灌胃辣椒素后再给予盐酸文拉法辛(实验组)的药动学差异。采用已验证的液相色谱-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,SPSS软件计算两组实验的差异是否具有显著性。结果:对照组和实验组大鼠血浆中文拉法辛的AUC0-10、Cmax、Tmax、 t1/2分别为(780.81±709.76)μg·L-1·h-1和(1037.84±582.63)μg·L-1·h-1、(517.57±462.46)μg·L-1和(876.64±301.79)μg·L-1、(0.32±0.20) h和(0.25±0.09) h、(1.00±0.84) h和(0.89±0.18) h;O-去甲基文拉法辛的AUC0-10、Cmax、Tmax、 t1/2分别为(163.60±77.93)μg·L-1·h-1和(240.41±62.69)μg·L-1·h-1、(96.83±46.51)μg·L-1和(182.52±46.40)μg·L-1、(0.46±0.30) h和(0.25±0.06) h、(1.19±0.32) h和(2.65±1.58)h;其中实验组的AUC0-10、Cmax均增加,差异具有显著性。结论:辣椒素增加文拉法辛的吸收,提高生物利用度,即能影响文拉法辛的体内药动学过程。

OBJECTIVE To investigate the effect of capsaicin on the pharmacokinetics of venlafaxine and its active metabolite O-desmethyl venlafaxine. METHODS enlafaxine hydr-ochloride was given to 10 healthy SD rats at a single dose(20.25 mg·kg^-1)(control group) and then capsaicin wasere given for 7 days(test group) to observe pharmacokinetic differences by using self-control method. The plasma concentrations of venlafaxine and O-desmethyl venlafaxine were determined by verified liquid chromatography-tandem mass spectrometry(LC-MS/MS). The pharmacokinetic parameters were calculated by DAS 3.2.4 software, and through SPSS software to find out whether the two groups had statistically significance. RESULTS The AUC0-10, Cmax, Tmax, and t1/2 of plasma venlafaxine in rats of the control and experimental groups were(780.81±709.76) μg·L-1·h-1 and(1 037.84±582.63) μg·L^-1·h^-1,(517.57±462.46) μg·L^-1 and(876.64±301.79) g·L^-1,(0.32±0.20) h and(0.25±0.09) h,(1.00±0.84) h and(0.89±0.18) h, respectively. One the other hand, the AUC0-10, Cmax, Tmax, and t1/2of plasma O-desmethyl venlafaxine in rats of the control and experimental groups were(163.60±77.93) g·L^-1·h^-1 and(240.41±62.69) μg·L^-1·h^-1,(96.83±46.51) μg·L^-1 and(182.52±46.40) μg·L^-1,(0.46±0.30) h and(0.25±0.06) h,(1.19±0.32) h and(2.65±1.58) h, respectively. Both AUC0-10 and Cmax were increased in test group, and the difference had statistical significance. CONCLUSION Capsaicin increases the absorption and the bioavailability of venlafaxine, so it can affect the in vivo pharmacokinetics of venlafaxine.