艾司唑仑片在中国健康受试者中的药代动力学及生物等效性研究  

Pharmacokinetics and bioequivalence studies of two estazolam tablet formulations in Chinese healthy volunteers

作　　者：刘岳[1] 刘晓慧 齐文渊[1] 丛端端 王娟 李鸿艳[1] 赵飞 田玉林[2] 李可欣[1] 薛薇[1] LIU Yue;LIU Xiao-hui;QI Wen-yuan;CONG Duan-duan;WANG Juan;LI Hong-yan;ZHAO Fei;TIAN Yu-lin;LI Ke-xin;XUE Wei(Clinical Trial Center,Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Science,Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation,Beijing 100730,China;Huazhong Pharmaceutical Co.,Ltd.,Xiangyang 441100,Hubei Province,China)

机构地区：[1]北京医院临床试验研究中心、国家老年医学中心、中国医学科学院老年医学研究所、药物临床风险与个体化应用评价北京市重点实验室,北京100730 [2]华中药业股份有限公司,湖北襄阳441100

出　　处：《中国临床药理学杂志》2021年第14期1776-1779,1784,共5页The Chinese Journal of Clinical Pharmacology

基　　金：“十三五”新药创制重大专项基金资助项目(2017zx09304026,2017zx09101001-002)。

摘　　要：目的研究艾司唑仑片仿制药与原研药在中国健康受试者中单剂量空腹及餐后给药的生物等效性。方法研究采用单中心、单剂量、随机、开放、两周期、两序列、双交叉试验设计,评价两制剂空腹及餐后状态下的生物等效性。空腹及餐后试验各纳入24例健康受试者,受试者每周期口服艾司唑仑片1 mg。用液相色谱-串联质谱(LC-MS/MS)法测定血浆中艾司唑仑的浓度,用Phoenix WinNonlin 6.4计算药代动力学参数。结果空腹试验中受试药物和参比药物的主要药代动力学参数:C_(max)分别为(61.25±10.98),(59.93±10.62)ng·mL^(-1);T_(max)分别为0.50(0.25,3),1.00(0.25,2)h;AUC_(0-t)分别为(1442.39±369.63),(1454.11±413.79)h·ng·mL^(-1);AUC_(0-∞)分别为(1523.89±428.93),(1525.65±490.00)h·ng·mL^(-1)。C_(max)的几何均值比的90%置信区间分别为96.16%~108.43%、96.25%~103.56%和94.77%~102.64%,均符合生物等效性的等效范围要求。餐后试验中受试药物和参比药物的主要药代动力学参数:C_(max)分别为(45.89±5.96),(42.34±7.94)ng·mL^(-1);T_(max)分别为3.00(1,8)h,3.00(1,5)h;AUC_(0-t)分别为(1417.11±353.34),(1411.85±344.77)h·ng·mL^(-1);AUC_(0-∞)分别为(1541.50±376.57),(1516.33±418.99)h·ng·mL^(-1)。C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值比的90%置信区间分别为104.50%~115.75%,99.08%~107.15%和98.10%~106.86%,均符合生物等效性的等效范围要求。结论两个厂家的艾司唑仑片具有生物等效性。Objective To compare the pharmacokinetics and bioequivalence of estazolam tablet test products and reference products in Chinese healthy subjects after single oral administration.Methods A single-center,single-dose,randomized,open-label,two period crossover study was designed.A total of 24 subjects in fasting state and 24 subjects in fed state were given single oral dose 1 mg of test and reference estazolam tablets.The plasma concentration of estazolam was assayed by LC-MS/MS.The pharmacokinetic parameters were calculated by WinNonlin 6.4 software.Results The major pharmacokinetic parameters of the test and reference preparations in the fasting test were as follows:Cmax(61.25±10.98)and(59.93±10.62)ng·mL^(-1),T_(max)0.50(0.25,3)and 1.00(0.25,2)h,AUC_(0-t)(1442.39±369.63)and(1454.11±413.79)h·ng·mL^(-1),AUC_(0-∞)(1523.89±428.93)and(1525.65±490.00)h·ng·mL^(-1).The 90%confidence intervals for the ratios of Cmax,AUC_(0-t),AUC_(0-∞)were 96.16%-108.43%,96.25%-103.56%and 94.77%-102.64%,respectively,which all met the predetermined criteria for assuming bioequivalence.The major pharmacokinetic parameters of the test and reference preparations in the fed condition were as follows:Cmax(45.89±5.96)and(42.34±7.94)ng·mL^(-1),T_(max)3.00(1,8)and 3.00(1,5)h,AUC_(0-t)(1417.11±353.34)and(1411.85±344.77)h·ng·mL^(-1),AUC_(0-∞)(1541.50±376.57)and(1516.33±418.99)h·ng·mL^(-1).The 90%confidence intervals for the ratios of Cmax,AUC_(0-t),AUC_(0-∞)were 104.50%-115.75%,99.08%-107.15%and 98.10%-106.86%,respectively,which all met the predetermined criteria for assuming bioequivalence.Conclusion These results indicate that two formulations of estazolam are bioequivalent.

关 键 词：艾司唑仑片 生物等效性 药代动力学 高效液相色谱-质谱联用法 

分 类 号：R971[医药卫生—药品]