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目的探究高脂饮食及性别差异对托伐普坦在人体内药动学的影响,指导临床合理用药。方法采用随机、双周期交叉自身对照设计,将30名健康志愿者(男∶女=1∶1)随机分成2组,分别于高脂或空腹口服托伐普坦片30 mg,采集血样并采用LC-MS/MS法测定血浆中托伐普坦的浓度。用SAS 9.3药动学软件进行药动学参数计算及统计学分析。结果高脂组与空腹组给药的主要药动学参数相比,ρmax和t1/2具有显著差异(P<0.05),而tmax、AUC无统计学差异(P>0.05);男女性别之间无论在高脂组还是空腹组相比,其主要药动学参数AUC、t1/2、ρmax、tmax在性别间均无统计学差异(P>0.05)。结论高脂饮食可显著提高托伐普坦的峰质量浓度(ρmax)并显著缩短其消除期的半衰期(t1/2);而无论是高脂或空腹口服托伐普坦片,性别差异均不影响其药动学参数。
Objective To investigate the effects of high fat diet and gender differences on pharmacokinetics of tolvaptan in the human body and to guide clinical rational drug use. Methods 30 healthy volunteers (male: female = 1: 1) were randomized into two groups randomly by a randomized, two-cycle crossover self-control design. The patients were orally given 30 mg of tolvaptan respectively for high fat or fasting, Determination of plasma concentration of tolvaptan by LC-MS / MS method. Pharmacokinetic parameters and statistical analysis with SAS 9.3 pharmacokinetics software. Results Compared with the main pharmacokinetic parameters of fasting group, there were significant differences in pmax and t1 / 2 (P <0.05) and no significant difference in tmax and AUC (P> 0.05) between male and female subjects The main pharmacokinetic parameters AUC, t1 / 2, ρmax and tmax were not significantly different between the two sexes (P> 0.05). Conclusion High-fat diet can significantly increase the peak mass concentration of tolvaptan (pmax) and shorten its elimination half-life (t1 / 2) significantly. However, both high-fat or fasting orally taken tolvaptan tablets did not show gender differences Affect its pharmacokinetic parameters.