阿斯达莫缓释胶囊的人体生物等效性研究

Relative bioavailability of dipyridamole compound recipe extended-release capsules in healthy volunteers

目的 比较阿斯达莫缓释胶囊在20名健康志愿者体内的药动学特征及相对生物利用度,评价其生物等效性。 方法20名健康男性志愿者采用随机交叉给药方案。单剂量试验中分别口服受试制剂——阿斯达莫缓释胶囊2粒 (每粒含双嘧达莫100 mg和阿司匹林12．5 mg)或参比制剂——双嘧达莫片8片(25 mg·片-1)及阿司匹林肠溶 片1片(25 mg·片-1)。多剂量试验中,分别口服试验制剂阿斯达莫缓释胶囊,2次·d-1,1粒·次-1和参比制剂 双嘧达莫片,3次·d-1,2片·次-1,连服5 d。采用高效液相色谱-质谱联用的方法测定双嘧达莫及水杨酸的血药 浓度,计算两者的药物动力学参数,评价生物等效性。结果单剂量试验,受试制剂及参比制剂中水杨酸和双嘧达 莫的药物动力学参数经统计学分析,两制剂生物等效。多剂量试验,受试制剂及参比制剂中双嘧达莫的药物动力学 参数经折算后进行统计学分析,结果表明试验制剂Cmax、Cmin、Css、DF均符合缓释特点。结论 口服试验制剂阿 斯达莫缓释胶囊剂2次·d-1,与口服等剂量市售双嘧达莫普通片以及阿司匹林肠溶片3次·d-1,具有生物等效性。

OBJECTIVE To determine the pharmacokinetics and relative bioavailability of dipyridamole compound recipe extended release capsules. METHODS Twenty healthy volunteers were recruited in a randomized crossover design. In the single-dose test, they respectively took test drug-dipyridamole compound recipe 2 pills （each pill has 100 mg dipyridamole and 12.5 mg aspirin） or reference drug dipyridomale 8 pills （25 mg/pill） and aspirin l pill （25 mg/pill）. In the multi dose test volunteers respectively took test drug （1 pill, bid） or reference drug （dipyridomale 50 mg, tid） for five days. The plasma concentrations of dipyridamole and salicylic acid were determined by HPLC-MS method. RESULTS In the single-dose test the main pharmacokinetic parameters of salicylic acid and dipyridamole were tested by statistics analysis. The two preparations were bioequivalent. In the multi dose test, the main pharmacokinetic paramenters of dipyridamole had been converted and showed they were bioequivalent. The Cmax, Cmin, Css, and DF of the test preparation had sustained-release features. CONCLUTIONS It is bioequivalent to take the test preparation twice every day orally or take the same dose of the reference drugs 3 times a day.