利伐沙班片在中国健康受试者中的药动学及生物等效性评价  

Pharmacokinetics and bioequivalence of rivaroxaban tablet in Chi-nese healthy subjects

作　　者：解染 程璐 周双[1] 张雪媛 王晓如[4] 赵侠[1,2] 何旭[1,5,6] 赵楠 贾博[1,2] 崔一民[1,6] XIE Ran;CHENG Lu;ZHOU Shuang;ZHANG Xueyuan;WANG Xiaoru;ZHAO Xia;HE Xu;ZHAO Nan;JIA Bo;CUI Yimin(Department of Pharmacy,Peking University First Hospital,Beijing 100034,China;Drug Clinical Trial institution,Peking University First Hospital,Beijing 100034,China;Shanghai Innovstone Therapeutics Limited,Shanghai 201318,China;CSPC Zhongqi Pharmaceutical Technology(Shijiazhuang)Co.,Ltd.Shijiazhuang 050000,Hebei,China;Institute of Clinical Pharmacology,Peking University First Hospital,Beijing 100034,China;Administration and Clinical Pharmacy School of Phar-maceutical Science,Department of Pharmacy,Peking University,Beijing 100191,China)

机构地区：[1]北京大学第一医院药学部,北京100034 [2]北京大学第一医院药物临床试验机构,北京100034 [3]上海海翊石医药科技有限公司,上海201318 [4]石药集团中奇制药技术(石家庄)有限公司,河北石家庄050000 [5]北京大学第一医院临床药理研究所,北京100034 [6]北京大学药学院药事管理与临床药学系,北京100191

出　　处：《中国临床药理学与治疗学》2024年第11期1295-1299,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家科技重大专项—重大新药创制课题资助项目(2017ZX09101001)。

摘　　要：目的:评价利伐沙班片在人体中的生物等效性。方法:空腹和餐后组各入选28例健康受试者,试验采用四周期、完全重复交叉设计,各周期服药剂量为10 mg(受试制剂T或参比制剂R)。采用HPLC-MS/MS测定血样中利伐沙班的浓度。采用Phoenix WinNonlin 7.0软件计算相关药代动力学(PK)参数,进而评价两制剂是否等效。结果:空腹组T和R两制剂的Cmax分别为(186.57±56.41)、(187.61±50.89)ng/mL;AUC0-t分别为(1 156.21±335.85)、(1 177.59±343.72)h·ng·mL^(-1);AUC0‐∞分别为(1 235.77±384.03)、(1 223.53±392.10)h·ng·mL^(-1)。两制剂的上述三个PK参数几何均值比(GMR)的90%置信区间(CI)分别为90.81%~105.67%,92.83%~103.85%,95.04%~107.13%;个体内变异比率90%CI上限值分别为1.56、1.41、1.73。餐后组T和R两制剂的Cmax分别为(207.81±45.26)、(211.04±36.62)ng/mL;AUC0-t分别为(1 271.26±260.92)、(1 233.23±201.85)h·ng·mL^(-1);AUC0‐∞分别为(1 290.76±264.90)、(1 251.68±203.73)ng·h·mL^(-1)。两制剂的上述三个PK参数GMR 90%CI分别为92.82%~102.28%,97.68%~106.68%,97.71%~106.68%;个体内变异比率90%CI上限值分别为1.76、1.47、1.47。结论:两种利伐沙班片在人体内生物等效。AIM:To evaluate the bioequivalence of the two rivaroxaban tablets in Chinese healthy subjects.METHODS:Twenty-eight subjects under fasting status and twenty-eight subjects under fed status were enrolled in the study.This study was designed as a four period,fully repetitive,cross-over study.All subjects were administered test(T)and reference(R)rivaroxaban tablets(10 mg)un-der fasting and fed condition respectively.Liquid chromatography-tandem mass spectrometry was used to detect the concentrations of rivaroxaban in plasma.WinNonlin 7.0 was used to calculate the main pharmacokinetic parameters(PK)and to eval-uate the bioequivalence.RESULTS:In fasting group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(186.57±56.41)and(187.61±50.89)ng/mL;AUC0-t were(1156.21±335.85)and(1177.59±343.72)h·ng·mL^(-1);AUC0‐∞were(1235.77±384.03)and(1223.53±392.10)ng·h·mL^(-1).The 90%confidential interval(CI)of the three main parameters were 90.81%-105.67%,92.83%-103.85%and 95.04%-107.13%.The upper limit of the 90%CI for the test-to-reference ratio of the within-subject of Cmax,AUC0-t and AUC0‐∞were 1.56,1.41 and 1.73.In fed group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(207.81±45.26)and(211.04±36.62)ng/mL;AUC0-t were(1271.26±260.92)and(1233.23±201.85)h·ng·mL^(-1);AUC0‐∞were(1290.76±264.90)and(1251.68±203.73)ng·h·mL^(-1).The 90%CI of the three main parameters were 92.82%-102.28%,97.68%-106.68%and 97.71%-106.68%.The upper limit of the 90%CI for the test-to-reference ratio of the within-subject of Cmax,AUC0-t and AUC0‐∞were 1.76,1.47 and 1.47.CONCLUSION:The two preparations of rivaroxaban tablets were bioequiva-lent.

关 键 词：利伐沙班 生物等效性 窄治疗窗药物 

分 类 号：R969[医药卫生—药理学]