双醋瑞因胶囊在健康受试者中的餐后生物等效性研究

Study on postprandial bioequivalence of Diacerein capsules in healthy volunteers

目的评价健康受试者餐后口服两种双醋瑞因胶囊的生物等效性。方法共纳入24名成年健康受试者,随机分为两组,每组12名。采用随机、开放、双周期交叉试验设计,两组患者于每周期试验首日早晨进食标准餐30 min后,分别口服受试制剂(国产双醋瑞因胶囊)和参比制剂(安必丁®)50 mg,清洗期为1周。分别于服药前后不同时间点采集血样,用甲醇沉淀蛋白进行样品前处理,以大黄素为内标,采用液相色谱-串联质谱法测定活性代谢产物大黄酸的质量浓度,采用DAS 3.2.9软件计算其药动学参数并进行生物等效性评价。结果受试者餐后服用受试制剂和参比制剂后,其体内大黄酸的c_(max)分别为(3517±1121)、(3225±755)ng/mL,AUC_(0-24 h)分别为(25764±6134)、(24316±5856)ng·h/mL,AUC_(0-∞)分别为(26679±6409)、(25170±6415)ng·h/mL,t_(max)分别为3.50(0.67,12.00)、4.00(1.50,7.00)h,t_(1/2)分别为(4.26±1.12)、(4.19±1.05)h;两制剂c_(max)、AUC_(0-24 h)、AUC_(0-∞)几何均值比的90%置信区间分别为100.8%~113.9%、103.1%~109.4%、103.2%~109.9%。结论在健康受试者餐后状态下,受试制剂与参比制剂生物等效。

OBJECTIVE To evaluate the postprandial bioequivalence of two kinds of Diacerein capsules in healthy volunteers with oral administration.METHODS A total of 24 adult healthy subjects were included and randomly divided into two groups,with 12 subjects in each group.A randomized,open,double-cycle cross-over trial design was adopted.Both groups took 50 mg of the test preparation(domestic Diacerein capsules)or the reference preparation(Ambridine®)respectively at 30 min after eating the standard meal in the morning of the first day of each cycle of the trial.The cleaning period was one week.Blood samples were collected at different time points before and after taking the medicine and the protein was precipitated with methanol for sample pretreatment.The concentration of active metabolite rhein was determined by LC-MS/MS using emodin as internal standard.The pharmacokinetic parameters were calculated with DAS 3.2.9 software,and the bioequivalence of test and reference preparation were evaluated.RESULTS After the subjects took the test preparation and the reference preparation after meal,the main pharmacokinetic parameters of rhein were as follows:cmax were(3517±1121)and(3225±755)ng/mL;AUC_(0-24 h) were(25764±6134)and(24316±5856)ng·h/mL;AUC_(0-∞) were(26679±6409)and(25170±6415)ng·h/mL;t_(max) were 3.50(0.67,12.00)and 4.00(1.50,7.00)h;t_(1/2) were(4.26±1.12)and(4.19±1.05)h,respectively.The 90%confidence intervals of the geometric mean ratios of c_(max),AUC_(0-24 h) and AUC_(0-∞) were 100.8%-113.9%,103.1%-109.4%and 103.2%-109.9%,respectively.CONCLUSIONS The test preparation and reference preparation are bioequivalent in the postprandial state of healthy subjects.