抑乳调经颗粒对奥氮平在大鼠体内药动学的影响

Effects of Yiru tiaojing granules on the pharmacokinetics of olanzapine in rats

目的探讨抑乳调经颗粒对奥氮平在大鼠体内药动学的影响。方法分别按单剂量给药和多剂量给药,将SD大鼠随机分4组,每组6只。A、B组大鼠分别单次灌胃奥氮平(5 mg/kg)、奥氮平(5 mg/kg)+抑乳调经颗粒(0.972 g/kg);C、D组大鼠同法给药,每天1次,连续给药14 d。分别在给药前及末次给药后5、15、30 min和1、2、3、6、8、12、24 h于大鼠眼眶静脉丛采血,采用液相色谱-质谱技术测定大鼠的血药浓度,采用DAS 2.0软件计算药动学参数。结果与A组比较,B组大鼠24 h内的药-时曲线下面积(AUC_(0-24 h))、AUC_(0-∞)、峰浓度(c_(max))均显著降低(P<0.05),24 h内的平均滞留时间(MRT_(0-24) h)、MRT_(0-∞)、表观清除率(CLz/F)均显著延长(P<0.05);C组与D组大鼠的药动学参数比较,差异均无统计学意义(P>0.05)。结论单次联用抑乳调经颗粒会抑制奥氮平在大鼠体内的吸收,长期联用抑乳调经颗粒对奥氮平的药动学过程无明显影响。

OBJECTIVE To investigate the effects of Yiru tiaojing granules on the pharmacokinetics of olanzapine in rats.METHODS SD rats were randomly divided into 4 groups according to single-dose administration and multiple-dose administration,with 6 rats in each group.Groups A and B were given olanzapine(5 mg/kg)or olanzapine(5 mg/kg)+Yiru tiaojing granules(0.972 g/kg)in a single gavage,and groups C and D were administered with the same method once a day for 14 d.Blood was collected from the orbital venous plexus before administration and 5,15,30 min and 1,2,3,6,8,12,24 h after the last administration,respectively.The blood concentration was determined by LC-MS,and the pharmacokinetic parameters were calculated by using DAS 2.0 software.RESULTS Compared with group A,group B showed a significant decrease in AUC_(0-24 h),AUC_(0-∞)and c_(max)(P<0.05),and a significant prolongation of MRT_(0-24 h),MRT_(0-∞)and CLz/F(P<0.05);there was no statistically significant difference in the pharmacokinetic parameters between group C and group D(P>0.05).CONCLUSIONS A single administration of Yiru tiaojing granules can inhibit the absorption of olanzapine in rats,and long-term administration of Yiru tiaojing granules does not have a significant effect on the pharmacokinetic process of olanzapine.