摘要
目的:建立高效液相色谱-串联质谱法(HPLC-MS/MS)测定人血浆中瑞舒伐他汀的浓度,研究瑞舒伐他汀钙片在我国健康受试者中的药动学特征,并评价其生物等效性。方法:采用随机、开放、两序列、两周期交叉给药试验设计,空腹组和餐后组分别纳入30例健康受试者,受试者单次口服瑞舒伐他汀钙片受试药物或参比药物10 mg,采用HPLC-MS/MS法测定血浆中瑞舒伐他汀的浓度,使用Phoenix WinNonlin 8.1软件计算药动学参数,评价生物等效性。结果:单次空腹给药受试药物、参比药物后,瑞舒伐他汀的主要药动学参数如下,C_(max)分别为(9.31±4.77)、(9.68±4.64)ng/mL;t_(max)分别为(4.37±0.73)、(4.25±0.95)h;t_(1/2)分别为(7.76±2.01)、(8.37±2.88)h;AUC_(0-72h)分别为(83.95±43.46)、(88.85±49.52)ng·h/mL;AUC_(0-∞)分别为(86.50±43.63)、(91.23±49.52)ng·h/mL。单次餐后给药受试药物、参比药物后,瑞舒伐他汀的主要药动学参数如下,C_(max)分别为(5.09±2.29)、(5.28±2.30)ng/mL;t_(max)分别为(4.45±0.90)、(4.47±1.22)h;t_(1/2)分别为(10.05±3.36)、(9.69±2.39)h;AUC_(0-72h)分别为(64.24±33.27)、(66.83±32.68)ng·h/mL;AUC_(0-∞)分别为(67.42±33.83)、(70.14±33.68)ng·h/mL。瑞舒伐他汀的主要药动学参数C_(max)、AUC_(0-72h)和AUC_(0-∞)几何均数比值(T/R)的90%CI在空腹状态下分别为91.46%~101.61%、91.59%~102.31%和91.91%~102.16%;餐后状态下分别为91.39%~103.73%、90.64%~101.61%和90.94%~101.45%。结论:本研究建立的HPLC-MS/MS法能快速、准确测定人血浆中瑞舒伐他汀的浓度;空腹和餐后状态下,2种瑞舒伐他汀钙片的主要药动学参数相近,具有生物等效性。
OBJECTIVE:To establish the liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for the determination of rosuvastatin in human plasma,study the pharmacokinetic characteristics of Rosuvastatin calcium tablets in healthy Chinese subjects and evaluate its bioequivalence.METHODS:The random,open,two-sequence,two-period,cross-over pharmacokinetic study method was adopted,30 healthy subjects were respectively enrolled in the fasting group and the postprandial group.Subjects received a single oral dose of Rosuvastatin calcium tablets subject drug or reference drug for 10 mg.The concentrations of rosuvastatin in plasma were determined by HPLC-MS/MS,and the pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.1 software to evaluate the bioequivalence.RESULTS:The main pharmacokinetic parameters of rosuvastatin after a single fasting dose of the test drug and the reference drug were as follows:the C_(max) were respectively(9.31±4.77)and(9.68±4.64)ng/mL;t_(max) were respectively(4.37±0.73)and(4.25±0.95)h;t_(1/2) were respectively(7.76±2.01)and(8.37±2.88)h;AUC_(0-72h) were respectively(83.95±43.46)and(88.85±49.52)ng·h/mL;AUC_(0-∞)were respectively(86.50±43.63)and(91.23±49.52)ng·h/mL.The main pharmacokinetic parameters of resulvastatin after single postprandial administration of the test drug and the reference drug were as follows:C_(max) were respectively(5.09±2.29)and(5.28±2.30)ng/mL;t_(max) were respectively(4.45±0.90)and(4.47±1.22)h;t_(1/2) were respectively(10.05±3.36)and(9.69±2.39)h;AUC_(0-72h) were respectively(64.24±33.27)and(66.83±32.68)ng·h/mL;AUC_(0-∞)were respectively(67.42±33.83)and(70.14±33.68)ng·h/mL.The 90%CI of T/R of C_(max),AUC_(0-72h) and AUC_(0-∞)of main pharmacokinetic parameters of rosuvastatin in fasting condition were from 91.46%to 101.61%,from 91.59%to 102.31%,from 91.91%to 102.16%;in fed condition were from 91.39%to 103.73%,from 90.64%to 101.61%,from 90.94%to 101.45%.CONCLUSIONS:The established HPLC-MS/MS method is rapid and accurate for the deter
作者
谢朋飞
陈元璐
崔宏娣
龙辉
张永东
侯思雨
周燕
周长欣
王本伟
XIE Pengfei;CHEN Yuanlu;CUI Hongdi;LONG Hui;ZHANG Yongdong;HOU Siyu;ZHOU Yan;ZHOU Changxin;WANG Benwei(PhaseⅠClinical Centre,Chenzhou No.1 People’s Hospital,Hunan Chenzhou 423000,China;Dept.of Research and Development,Shanxi Lanhua pharmaceutical Co.,Ltd,Shanxi Gaoping 048402,China;Dept.of Clinical Research,Anhui Wanbang Pharmaceutical Technology Co.,Ltd,Hefei 230601,China;Dept.of Biological Sample Analysis and Detection,Shandong Angile Bioassay Technologies Co.,Ltd,Jinan 250101,China)
出处
《中国医院用药评价与分析》
2022年第9期1036-1041,共6页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
国家科技重大专项-重大新药创制基金资助项目(No.2020ZX09201010)
南华大学医院管理研究所项目(No.2020YJGL06)
郴州市科技发展计划基金资助项目(No.yfzx201912)。
