丙戊酸钠对丹参酮ⅡA在癫痫大鼠体内药动学的影响

Effect of Sodium Valproate on Pharmacokinetics of Tanshinone IIA in Epileptic Rats

目的研究丙戊酸钠(VPA)对丹参酮IIA在癫痫大鼠体内药动力学的影响。方法采用锂-匹罗卡品建立癫痫大鼠模型,将造模成功的大鼠随机分为两组,分别灌胃生理盐水和VPA(189 mg/kg)连续7 d,于第8天给药丹参酮IIA(60 mg/kg)后,按不同时间点采集血样,采用超高效液相色谱—三重四级杆串联质谱(UPLC-MS/MS)测定丹参酮IIA在大鼠血浆中的含量,计算药动学参数。结果与丹参酮IIA单独给药组比较,丹参酮IIA+VPA组的血药浓度-时间曲线下面积(AUC)和达峰浓度(Cmax)明显增加(P<0.01),平均滞留时间(MRT)和半衰期(t1/2)延长(P<0.05),同时清除率(CL)显著减小(P<0.01)。结论VPA可以增加丹参酮IIA在癫痫大鼠体内的血药浓度,提高丹参酮IIA的生物利用度,影响丹参酮IIA在癫痫大鼠体内的药动学过程。

Objective To study the effect of sodium valproate(VPA)on pharmacokinetics of tanshinone IIA in epileptic rats.Methods A model of epileptic rats are established by using lithium-pilocarpine.The epileptic rats are randomly divided into tanshinone IIA group and tanshinone II+VPA group,normal saline and VPA(189 mg/kg)are administered for 7 d,respectively.After administration of tanshinone IIA(60 mg/kg)on the eighth day,blood samples are collected at different time points.UPLC-MS/MS method is used to determine the plasma concentration of tanshinone IIA in epilepsy rats,and pharmacokinetic parameters are calculated.Results Compared with the pharmacokinetic parameters of tanshinone IIA group,the area under concentrationtime curve(AUC)and peak concentration(Cmax)of tanshinon IIA+VPA group increased significantly(P<0.01),mean residence time(MRT)and half-life period(t1/2)prolonged(P<0.05),while clearance(CLz/F)decreased significantly(P<0.01).Conclusion VPA can increase the plasma concentration of tanshinone IIA,enhance the bioavailability,and affect the pharmacokinetic process of tanshinone IIA in epileptic rats.