摘要
目的:研究两种不同生产厂家的利伐沙班片在健康受试者中空腹和餐后状态下的生物等效性。方法:采用单中心、随机、开放、空腹和餐后、四周期、完全重复交叉试验设计。空腹和餐后状态下各28例健康男性和女性受试者,每周期分别口服受试制剂或参比制剂1片(10 mg),周期间的清洗期为7 d,用液相色谱串联质谱(LC-MS/MS)法测定受试者血浆(肝素钠)中利伐沙班浓度,使用Phoenix WinNonlin 7.0软件,计算各药代动力学(PK)参数,对受试制剂和参比制剂进行生物等效性评价。结果:空腹组:受试者口服试验用药品后,受试制剂和参比制剂的C_(max)分别为(200.96±68.99)ng/mL和(196.96±50.97)ng/mL,AUC_(0-t)分别为(1439.93±493.94)h·ng·mL^(-1)和(1395.90±411.49)h·ng·mL^(-1),AUC_(0-∞)分别为(1506.56±511.47)h·ng·m L^(-1)和(1451.94±417.89)h·ng·mL^(-1),C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比值(GMR)的90%置信区间(CI)分别为91.87%~103.37%、95.00%~105.07%、95.33%~105.57%,C_(max)、AUC_(0-t)、AUC_(0-∞)个体内标准差比值(S_(WT)/S_(WR))的90%CI分别为0.88~1.73、0.74~1.45、0.72~1.41。餐后组:受试者口服试验用药品后,受试制剂和参比制剂的C_(max)分别为(241.23±54.44)ng/m L和(226.54±48.04)ng/mL,AUC_(0-t)分别为(1383.26±437.05)h·ng·mL^(-1)和(1333.54±372.53)h·ng·mL^(-1),AUC_(0-∞)分别为(1404.01±439.89)h·ng·mL^(-1)和(1352.31±374.45)h·ng·mL^(-1),C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比值的90%CI分别为100.92%~110.50%、98.30%~108.31%、98.46%~108.39%,C_(max)、AUC_(0-t)、AUC_(0-∞)个体内标准差比值的90%CI分别为0.63~1.29、0.78~1.61、0.79~1.61。结论:两种制剂在健康受试者中空腹和餐后状态下具有生物等效性。
AIM:Study on the bioequivalence of rivaroxaban tablets from two different manufacturers in healthy subjects under fasting and postprandial conditions.METHODS:Adopting a single center,randomized,open,fasting and postprandial,four cycle,fully repeated crossover trial design.28 healthy male and female subjects were given oral administration of either the test or reference formulation(10 mg)on an empty stomach or in a postprandial state,with a cleaning period of 7 days between cycles.The concentration of rivaroxaban in the plasma(heparin sodium)of the subjects was measured using liquid chromatography tandem mass spectrometry(LC-MS/MS),and pharmacokinetic(PK)parameters were calculated using Phoenix WinNonlin 7.0 software to evaluate the bioequivalence of the test and reference formulations.RESULTS:Fasting group:After oral administration of the investigational drug,the C_(max) of the test formulation and reference formulation were(200.96±68.99)ng/mL and(196.96±50.97)ng/mL,respectively,and the AUC_(0-t) were(1439.93±493.94)h·ng·mL^(-1)and(1395.90±411.49)h·ng·mL^(-1),respectively,the AUC0∞were(1506.56±511.47)h·ng·mL^(-1)and(1451.94±417.89)h·ng·mL^(-1),respectively,the 90%confidence intervals for the geometric mean ratios of C_(max),AUC_(0-t),and AUC0∞were 91.87%-103.37%,95.00%-105.07%,95.33%-105.57%,respectively,the 90%CI of the intra-individual standard deviation ratio(S_(WT)/S_(WR))for C_(max),AUC_(0-t),AUC0∞were 0.88-1.73,0.74-1.45 and 0.72-1.41,respectively.Postprandial group:After oral administration of the experimental drug,the C_(max) of the test and reference formulations were(241.23±54.44)ng/mL and(226.54±48.04)ng/mL,respectively,and the AUC_(0-t) were(1383.26±437.05)h·ng·mL^(-1)and(1333.54±372.53)h·ng·mL^(-1),respectively,the AUC0∞were(1404.01±439.89)h·ng·mL^(-1)and(1352.31±374.45)h·ng·mL^(-1),respectively,the 90%confidence intervals for the geometric mean ratios of C_(max),AUC_(0-t),and AUC_(0-∞)were 100.92%-110.50%,98.30%-108.31%,and 98.46%-108.39%,respectively,the 90%CI of the intra-individual standard deviation ratio(S_(WT)/S_(WR))for C_(max),AUC_(0-t) and AUC0∞were 0.63-1.29,0.78-1.61 and 0.79-1.61,respectively.CONCLUSION:Bioequivalence of the two preparations in fasting and postprandial state in healthy subjects.
作者
陈璐
李晓斌
马雯霞
谢红瑜
王文萍
CHEN Lu;LI Xiaobin;MA Wenxia;XIE Hongyu;WANG Wenping(Affiliated Hospital of Liaoning University of Traditional Chinese Medicine GCP Center Phase I Clinical Trial Ward,Shenyang 110032,Liaoning,China;Hangzhou Zhuyangxin Pharmaceutical Co.,Ltd,Hangzhou 310018,Zhejiang,China)
出处
《中国临床药理学与治疗学》
北大核心
2025年第6期789-795,共7页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
辽宁省“兴辽英才计划”(XLYC1802008)
辽宁省中药临床药物代谢动力学重点实验室资助项目(辽科发2005-16)。
