复方丹参滴丸对癫痫大鼠体内丙戊酸钠药动学的影响

Effect of Compound Danshen Dripping Pills to Valproate acid of Epileptic rats in vivo

目的:研究复方丹参滴丸与丙戊酸钠(VPA)联用对癫痫大鼠体内VPA浓度的影响。方法:将SD大鼠随机分为VPA和VPA+复方丹参滴丸组,大鼠采用脑立体定位技术向大鼠海马内注入红藻氨酸(KA)建立癫痫模型;模型成功点燃后,VPA+复方丹参滴丸组以85mg/kg灌胃给药7天后,两组大鼠再分别给予VPA(189mg/kg)。在不同时间点进行大鼠眼眶采血,通过UPLC-MS/MS法测定VPA血药浓度。结果:与单独使用VPA组相比,VPA+复方丹参滴丸组大鼠曲线下面积(AUC(0-8h)和AUC(0-∞))有显著性提高,清除率(CLZ/F)、峰浓度(Cmax)、达峰时间(Tmax)也有显著变化,半衰期(T1/2z)、表观分布容积(Vz/F)均有不同程度的提高。结论:复方丹参滴丸与VPA联合使用可增加VPA在癫痫大鼠体内的分布且可提高VPA的血药浓度。

Objective： To study the effect of combination of compound danshen dropping pill and sodium valproate（VPA） on the concentration of VPA in rats with epilepsy. Methods： SD rats were randomly divided into VPA and VPA combined with compound danshen dropping pill groups,kainic acid was injected into the hippocampus of rats by stereotaxic technique to establish epilepsy model. After the model was successfully ignited,the rats in group VPA combined with compound danshen dropping pill were administrated with compound danshen dropping pill（85 mg/kg） for seven days. The rats in two groups were then given VPA（189 mg/kg） at different time points to collect blood in orbit,then determin the concentration of VPA in plasma by UPLC-MS/MS. Results： Compared with the single VPA group,the AUC（0-8 h）and AUC（0-∞）of the VPA combined with compound danshen dropping pill group was significantly improved（P 〈 0. 01）,CLZ/F,Tmax,Cmaxwere also of statistical differences（P 〈 0. 05）. The T1/2 z,Vz/Fwere also improved in different degrees. Conclusion： Combined use of compound danshen dropping pill and VPA can increase the distribution of VPA in epileptic rats and increase the concentration of VPA.