醋酸地塞米松片在中国健康受试者中的生物等效性研究  

Study on bioequivalence evaluation of dexamethasone acetate tablets in Chinese healthy volunteers

作　　者：肖雷[1] 徐媛媛 黄晓青 张文 曹阳 谢晶 周焕[3] 黄顺旺 XIAO Lei;XU Yuanyuan;HUANG Xiaoqing;ZHANG Wen;CAO Yang;XIE Jing;ZHOU Huan;HUANG Shunwang(Department of Pharmacy,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui,China;Hefei Innovative Medical Technology Co.,Ltd.,Hefei 230088,Anhui,China;National Drug Clinical Trial Institution The First Affiliated Hospital of Bengbu Medical College,Bengbu 233000,Anhui,China)

机构地区：[1]安徽医科大学第一附属医院药剂科,安徽合肥230022 [2]合肥创新医药技术有限公司,安徽合肥230088 [3]蚌埠医学院第一附属医院临床试验研究中心,安徽蚌埠233000

出　　处：《中国临床药理学与治疗学》2023年第12期1365-1371,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省自然科学基金(2008085QH401)。

摘　　要：目的:评估中国健康成年受试者空腹及餐后口服醋酸地塞米松片受试制剂和参比制剂的生物等效性。方法:按照随机、开放、单剂量、两周期双交叉的生物等效性研究。空腹组纳入24名健康受试者,餐后组纳入32名健康受试者,每周期服用受试制剂(T)2片(0.75 mg/片)或参比制剂(R)3片(0.50 mg/片),共两周期。使用液相色谱-质谱联用技术对人血浆中醋酸地塞米松的浓度进行测定,采用WinNonlin 8.0软件按非房室模型对药代动力学参数进行计算,并对受试制剂与参比制剂二者的生物等效性进行评价。结果:受试者空腹状态下口服醋酸地塞米松片受试制剂与参比制剂后药代动力学参数如下:Tmax分别为1.13(0.50,4.00)和1.00(0.50,5.00)h,AUC0-t分别为(72.25±21.55)和(69.23±17.76)ng·mL^(-1)·h,Cmax分别为(14.53±4.51)和(14.52±3.68)ng/mL,AUC0-∞分别为(74.63±23.01)和(71.32±19.12)ng·mL^(-1)·h;受试者餐后状态下口服醋酸地塞米松片受试制剂与参比制剂后药代动力学参数如下:Tmax分别为2.00(1.00,4.50)和1.50(1.00,4.50)h,AUC0-t分别为(81.57±21.28)和(76.06±13.63)ng·mL^(-1)·h,Cmax分别为(12.14±3.21)和(11.93±2.78)ng/mL,AUC0-∞分别为(85.12±23.92)和(78.95±14.99)ng·m L^(-1)·h。在空腹和餐后条件下,醋酸地塞米松片受试制剂与参比制剂主要药代动力学参数的几何均值比的90%置信区间均在80.00%~125.00%。结论:在空腹和餐后条件下,受试制剂醋酸地塞米松片与参比制剂醋酸地塞米松片具有生物等效性。AIM:To assess the bioequivalence of oral dexamethasone acetate tablets between the test and reference formulations in healthy adult Chinese subjects on an empty stomach and after meals.METHODS:A randomized,open,single-dose,two-cycle double crossover bioequivalence study was followed.Twenty-four healthy subjects were included in the fasting group,and 32 healthy subjects were included in the postprandial group,taking 2 tablets(0.75 mg/tablet)of the test formu-lation(T)or 3 tablets(0.50 mg/tablet)of the refer-ence formulation(R)per cycle for two cycles.The concentrations of dexamethasone acetate in hu-man plasma were determined using liquid chroma-tography-mass spectrometry,and the pharmacoki-netic parameters were calculated according to the non-atrial model using WinNonlin 8.0 software.The bioequivalence of both the test formulation and the reference formulation was evaluated.RESULTS:The pharmacokinetic parameters after oral adminis-tration of dexamethasone acetate tablets in a fast-ed state in subjects with the reference formulation are as follows:Tmax 1.13(0.50,4.00)and 1.00(0.50,5.00)h,AUC0-t(72.25±21.55)and(69.23±17.76)ng·mL^(-1)·h,Cmax(14.53±4.51)and(14.52±3.68)ng/mL,AUC0‐∞(74.63±23.01)and(71.32±19.12)ng·mL^(-1)·h.The pharmacokinetic parameters after oral admin-istration of dexamethasone acetate tablets in the postprandial state in subjects were as follows:Tmax 2.00(1.00,4.50)and 1.50(1.00,4.50)h,AUC0-t(81.57±21.28)and(76.06±13.63)ng·mL^(-1)·h,Cmax(12.14±3.21)and(11.93±2.78)ng/mL,and AUC0‐∞(85.12±23.92)and(78.95±14.99)ng·mL^(-1)·h.The 90%confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters of the test formulation of dexamethasone acetate to the reference formulation ranged from 80.00%to 125.00%under both fasting and postprandial condi-tions.CONCLUSION:Under fasting and postprandi-al conditions,the test formulation of dexametha-sone acetate tablets was bioequivalent to the refer-ence formulation of dexamethasone acetate tab-lets.

关 键 词：醋酸地塞米松片 药代动力学 生物等效性 

分 类 号：R969.1[医药卫生—药理学]