川芎嗪、阿魏酸对延胡索乙素大鼠体内药动学的影响

Effects of tetramethylpyrazine and ferulic acid on pharmacokinetics of tetrahydropalmatine in rats

目的探讨川芎嗪、阿魏酸对延胡索乙素大鼠体内的药动学规律的影响。方法 32只SD大鼠,分为延胡索乙素(20mg/kg)组、延胡索乙素(20 mg/kg)+阿魏酸(50 mg/kg)组、延胡索乙素(20 mg/kg)+川芎嗪(30 mg/kg)组、延胡索乙素(20 mg/kg)+川芎嗪(30 mg/kg)+阿魏酸(50 mg/kg)组,各组单剂量ig给药,采用RP-HPLC法分别测定各组大鼠血浆中延胡索乙素的浓度,DAS2.0程序计算药动学参数。结果延胡索乙素与阿魏酸或者川芎嗪联合给药时,AUC0～t、和Cmax与延胡索乙素单独给药相比显著增加,tmax、t1/2和MRT0～t比延胡索乙素单独给药时显著延长(P<0.05);延胡索乙素同时与阿魏酸、川芎嗪二者联合给药时AUC0～t、MRT0～t、t1/2和tmax与延胡索乙素单独给药相比显著增大(P<0.05),而Cmax与延胡索乙素单独给药时相比无显著差异。结论阿魏酸、川芎嗪可以显著增加延胡索乙素在大鼠体内的吸收,并显著延长延胡索乙素在大鼠体内的作用时间。

Objective To investigate the effects of tetramethylpyrazine （TMP） and ferulic acid （FA） on pharmacokinetics of tetrahydropalmatine （THP） in rats. Methods Thirty-two Sprague-Dawley rats were randomly divided into four groups such as THP 20 mg.kg-1, THP 20 mg.kg-1 ＋ FA 50 mg·kg-1, THP 20 mg·kg-1 ＋ TMP 30 mg·kg-1, and THP 20 mg·kg-l ＋ FA50 mg·kg-1 ＋ TMP 30 mg·kg-l groups. All the rats were ig administered and then blood samples were obtained from fossa orbitalis at several time points. All the plasma concentration was analyzed by RP-I-IPLC method and the data were treated by DAS 2.0 program. Results Compared with THP alone, THP combined with TMP or FA could increase the AUC0~t, tmax, and Crnax, and prolong the t1/2 and MRTα （P 〈 0.05）. Compared with THP alone, THP combined with TMP and FA could increase the AUC0-t, MRT0-α t1/2, and tmax, but had no influence on the Cmax. Conclusion FA and TMP can prolong the action time of THP in rats, and increase of THP absorption in rats in vivo.