Lack of pharmacokinetic interaction between valproic acid and a traditional Chinese medicine, Paeoniae Radix, in healthy volunteers
Lack of pharmacokinetic interaction between valproic acid and a traditional Chinese medicine, Paeoniae Radix, in healthy volunteers
复制标题
DOI：
10.1046/j.1365-2710.2000.00313.x
复制
发表时间：
2000-12-01
影响因子：
2
通讯作者：
Yang, LL
中科院分区：
文献类型：
--
作者：
Chen, LC;Chou, MH;Yang, LL
背景与目的：在东方国家，除标准的抗癫痫药物外，还使用中药治疗癫痫。抗癫痫药物与中药的相互作用是临床应用中的一个潜在问题。丙戊酸（valproic acid， VPA）是临床上应用最广泛的抗癫痫药物之一，在某些癫痫患者中可与中药白芍（paoniae， PR）合用，本研究旨在探讨白芍对VPA药代动力学的影响。方法：采用随机、开放标签、双向交叉研究的方法研究VPA的药代动力学，6名健康志愿者采用交叉设计：(i)每天1次1.2 g芍药提取粉，连用7天，第7天服用1片200 mg VPA胃药片；（ii）第7天单独服用1片200 mg VPA胃药片。第7天获得连续血浆样本。用荧光偏振免疫分析法（FPIA）测定总VPA和游离VPA血浆浓度。安全措施包括实验室检测（血液学、血清化学和尿液分析）和不良事件监测。采用学生配对t检验对药代动力学参数进行统计学比较。结果：总体临床安全性令人满意。VPA的平均血药浓度在单独口服VPA后6 h和联合口服PR后3 ~ 4 h达到最大值，VPA血药浓度下降，半衰期分别为11.71 h和11.91 h。两组间VPA的药代动力学参数（t -max、C-max、AUC、t（1/2）、MRT、CL/F、V-d/F）均无统计学差异。VPA蛋白结合率也无显著差异。结论：PR对健康志愿者VPA的吸收、分布、代谢和消除无明显影响。
Background and objective: In addition to the standard antiepileptic drugs, traditional Chinese medicines (TCMs) are used for the treatment of epilepsy in oriental countries. The interactions between antiepileptic drugs and TCMs represent a potential problem in clinical application. Because valproic acid (VPA), one of the most widely prescribed antiepileptic drugs, may be administered concomitantly with Paeoniae Radix (PR), one of the famous TCMs, in some epileptic patients, the present study was conducted to evaluate the influences of PR on the pharmacokinetics of VPA.Method: The pharmacokinetics of VPA were investigated in a randomized, open-label, two-way crossover study, Six healthy volunteers received the following treatments in a crossover design: (i) 1.2 g extract powder of Paeoniae Radix once daily for 7 days and one 200 mg VPA gastro-resistant tablet on day 7 and (ii) one 200 mg VPA gastro-resistant tablet alone on day 7. Serial plasma samples were obtained on day 7. Total and free (unbound) VPA plasma concentrations were determined by fluorescence polarization immunoassay (FPIA). Safety measures included laboratory tests (haematology, serum chemistry and urinalysis) and adverse event monitoring. Statistical comparisons of pharmacokinetic parameters were performed with the Student paired t-test.Results: Overall clinical safety was satisfactory. The mean maximum plasma concentration of VPA was attained at within 6 h after oral administration of VPA alone and 3-4 h after oral administration of VPA in combination with PR. The plasma level of VPA declined with a half-life of 11.71 and 11.91 h, respectively. No statistically significant difference was obtained in any of the pharmacokinetic parameters (T-max, C-max, AUC, t(1/2), MRT, CL/F and V-d/F) of VPA between the two treatments. Also, there was no significant difference in the protein binding rates of VPA.Conclusion: PR did not significantly affect the absorption, distribution, metabolism and elimination of VPA in healthy volunteers.