HPLC法研究唑尼沙胺分散片在中国健康志愿者的药动学  

Pharmacokinetics of zonisamide dispersible tablets in healthy Chinese volunteers using an analytic method of HPLC

作　　者：戴青[1] 陈勇川[1] 邱学文[1] 向荣凤[1] 熊丽蓉[1] 

机构地区：[1]第三军医大学西南医院药剂科,国家药品临床研究基地,重庆400038

出　　处：《中国药物应用与监测》2014年第1期1-4,共4页Chinese Journal of Drug Application and Monitoring

基　　金：重庆市工程技术研究中心建设项目(CSTC2012PT-GC10007)

摘　　要：目的：建立人血浆唑尼沙胺浓度的测定方法,研究唑尼沙胺分散片在健康受试者体内的单、多剂量药动学.方法：30 名健康志愿者（男女各半）分3 组,分别单剂量（200、300、400 mg）口服唑尼沙胺分散片,300 mg 剂量组单剂量结束后继续进入多剂量研究,每日1 次,连续14 d.采用HPLC法测定血浆中唑尼沙胺的浓度,用DAS 2.1.1 软件计算药动学参数.结果：在200 ～400 mg 剂量范围内,唑尼沙胺的AUC0-t、AUC0-∞、Cmax 均与剂量呈线性关系,中剂量组多次给药后的药动学参数如下：Cmax 为（27.305 ± 5.201） μg·mL-1;tmax 为（2.556 ± 0.726） h;t1/2 为（59.286 ± 8.882） h;AUC0-t 为（2 435.713 ± 668.845）μg·h·mL-1;AUC0-∞ 为（2 522.230 ± 720.554） μg·h·mL-1.结论：男、女受试者单次给药后的Cmax存在显著性差异.唑尼沙胺在连续多次给药后,可达稳态血药浓度.Objective：To establish an HPLC method for the determination of zonisamide in human plasma, and studythe pharmacokinetics of zonisamide dispersible tablets with single and multiple doses in healthy Chinese volunteers. Methods：Thirty healthy volunteers were randomly divided into three groups. The volunteers in the three groups were given single-dose ofzonisamide dispersible tablets respectively with 200, 300 and 400 mg, and then those subjects in 300 mg single-dose zonisamidedispersible tablets group were enrolled for multiple-dose study, who were given zonisamide once a day for fourteen days. The plasmaconcentrations of zonisamide were determined by HPLC method, the pharmacokinetic parameters were calculated and analyzed byDAS 2.1.1 software. Results：AUC0-t, AUC0-∞ and Cmax of zonisamide increased in a linear manner at the dose range from 200 to400 mg. For the multiple-dose administration, the parameters were as follow： Cmax （27.305 ± 5.201） μg·mL-1, tmax （2.556 ± 0.726）h, t1/2 （59.286 ± 8.882） h, AUC0-t （2 435.713 ± 668.845） μg·h·mL-1, AUC0-∞ （2 522.230 ± 720.554） μg·h·mL-1. Conclusion： Cmaxshowed significant difference in physiological disposition between the male and female after administration of a single-dose. Afterthe administration of multiple-dose zonisamide, steady state plasma concentrations can be achieved.

关 键 词：唑尼沙胺 高效液相色谱法 血浆 药动学 

分 类 号：R969.1[医药卫生—药理学]