盐酸地芬尼多片在健康人体内的生物等效性研究  

Bioequivalence of difenidol hydrochloride tablets in healthy volunteers

作　　者：林凡友 李宁 孙永喜 陈仁燕 LIN Fan-you;LI Ning;SUN Yong-xi(Sunhover Pharmaceutical Co.,Ltd.,Linyi,Shandong 276023,China)

机构地区：[1]翔宇药业股份有限公司,山东临沂276023

出　　处：《中国处方药》2020年第10期1-3,共3页Journal of China Prescription Drug

摘　　要：目的评价盐酸地芬尼多片受试制剂与参比制剂的生物等效性,为临床使用和一致性评价提供依据。方法采用随机、开放、单剂量、交叉试验设计,将空腹和餐后各36例健康受试者随机分为两组,分别口服单剂量盐酸地芬尼多片受试制剂和参比制剂各25 mg,采用高效液相色谱-串联质谱(HPLC-MS/MS)测定受试者血浆中地芬尼多(DNP)的浓度,在试验期间对受试者的临床观察指标进行相关的安全性评价,并对两种制剂进行生物等效性评价,所有数据均采用SAS 9.4、Phoenix WinNonlin 8.0软件进行分析。结果用生物等效性的判断标准,空腹和餐后状态下受试制剂的Cmax、AUC0→t和AUC0→∞几何均值与参比制剂对应参数的比值的90%置信区间分别为85.22%~100.49%、89.47%~101.82%、89.76%~101.76%和87.28%~117.20%、99.28%~113.78%、98.98%~113.44%,均在80.00%~125.00%范围内,可以判断两种制剂具有生物等效性。此外,试验期间两制剂组的受试者均未发生Ⅲ级及以上不良事件,均未发生严重不良事件,均未因不良事件退出试验。结论盐酸地芬尼多片的受试制剂和参比制剂具有生物等效性,并且安全可靠。Objective To evaluate the bioequivalence of the test preparation and the reference preparation of difenidol hydrochloride tablets,so as to provide basis for clinical use and consistency evaluation.Methods Random,open,single dose and cross trial design were used,fasting and 36 postprandial 36 healthy subjects were randomly divided into two groups.Each group was given a single dose of difenidol hydrochloride tablets with 25 mg of test preparation and a reference preparation.The concentration of difenidol hydrochloride(DPN)in human plasma was determined by HPLC-MS/MS.During the trial,the safety of the clinical observation indexes of the subjects was evaluated,and the bioequivalence of the two preparations was evaluated.All the data were analyzed by SAS 9.4 and Phoenix WinNonlin 8.0 software,Results 90%confidence intervals of the ratio of geometric mean and reference preparation parameters under fasting and postprandial conditions respectively were 85.22%~100.49%,89.47%~101.82%,89.76%~101.76%and 87.28%~117.20%,99.28%~113.78%,98.98%~113.44%,within the range of 80.00%~125.00%according to criteria of bioequivalence.The results demonstrated the difenidol hydrochloride tablets between reference and test products were bioequivalent.In addition,during the test period,the subjects in the two preparation groups did not have gradeⅢor above adverse events,no serious adverse events,and no withdrawal from the test due to adverse events.Conclusion The test tablet and reference tablet of difenidol hydrochloride tablets were equivalent and safe.

关 键 词：盐酸地芬尼多片 生物等效性 空腹 餐后 

分 类 号：R969.1[医药卫生—药理学]