依折麦布片在中国健康受试者中的药代动力学和生物等效性研究  被引量:3

Pharmacokinetics and bioequivalence studies of ezetimibe tablets in healthy Chinese subjects

在线阅读下载全文

作  者:胡展晴 黄洁[1] 阳国平[1] 崔畅 张行飞 叶玲 阳晓燕[1] 杨双[1] HU Zhan-qing;HUANG Jie;YANG Guo-ping;CUI Chang;ZHANG Xing-fei;YE Ling;YANG Xiao-yan;YANG Shuang(Center of Clinical Pharmacology,The Third Xiangya Hospital,Central South University,Changsha 410013,Hunan Province,China)

机构地区:[1]中南大学湘雅三医院临床药理中心,湖南长沙410013

出  处:《中国临床药理学杂志》2022年第3期243-248,共6页The Chinese Journal of Clinical Pharmacology

基  金:“十三五”国家“重大新药创制”科技重大专项基金资助项目(2020ZX09201010);国家自然科学基金资助项目(81673519);湖南省自然科学基金青年基金资助项目(2020JJ5852)。

摘  要:目的研究空腹及餐后条件下单剂量依折麦布片的药代动力学特征,评价其生物等效性和安全性。方法空腹组和餐后组各入组48例健康受试者,采用单中心、单剂量、空腹/餐后、随机、开放、两制剂、两周期、双交叉的试验设计,每周期受试者单次空腹或餐后口服受试药物或参比药物依折麦布片10 mg,用HPLC-MS/MS法测定给药后不同时间点受试者血浆中依折麦布和总依折麦布(依折麦布+依折麦布-葡萄糖醛酸结合物)的浓度。采用非房室模型计算药代动力学参数,评价2种依折麦布的生物等效性。结果单次空腹给药受试药物与参比药物血浆中总依折麦布的主要药代动力学参数:C_(max)分别为(70.74±30.08)和(72.32±25.46)ng·mL^(-1);t_(max)分别为1.12和1.25 h;t_(1/2)分别为(14.02±7.40)和(13.75±6.88)h;AUC_(0-t)分别为(530.93±221.48)和(514.81±215.49)h·ng·mL^(-1);AUC_(0-∞)分别为(565.54±227.79)和(550.86±239.24)h·ng·mL^(-1)。单次餐后给药受试药物与参比药物血浆中总依折麦布的主要药代动力学参数:C_(max)分别为(109.78±49.31)和(112.33±40.73)ng·mL^(-1);t_(max)分别为2.00和1.50 h;t1/2分别为(15.50±8.76)和(13.36±6.61)h;AUC_(0-t)分别为(627.51±267.46)和(565.57±188.63)h·ng·mL^(-1);AUC_(0-∞)分别为(683.91±316.10)和(616.88±218.22)h·ng·mL^(-1)。受试药物和参比药物的主要药代动力学参数C_(max)、AUC_(0-t)、AUC_(0-∞)经对数转换后进行方差分析,在90%置信区间范围内,空腹状态下总依折麦布分别为88.90%~103.31%,97.84%~109.29%,96.66%~109.94%;餐后状态下总依折麦布分别为84.79%~103.87%,102.71%~112.92%,103.35%~115.71%。结论空腹和餐后状态下,健康受试者口服两种依折麦布的主要药代动力学参数相近,且安全性良好,具有生物等效性。Objective To study the pharmacokinetic characteristics of single-dose ezetimibe tablets under fasted and fed conditions,and to evaluate their bioequivalence.Methods Forty-eight healthy subjects were enrolled in fasted and fed groups.Single-center,single-dose,fasting/fed,randomized,open,two-preparation,two-period,and double-crossover experimental design was used.Test drug or reference drug ezetimibe tablets 10 mg were given on fasting or fed,HPLC-MS/MS was used to determine the plasma ezetimibe and total ezetimibe(total ezetimibe)at different time points after administration(the concentration of ezetimibe plus ezetimibe-glucuronic acid conjugate).The non-compartmental model was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test drug and the reference drug after a single fasted administration:C_(max) were(70.74±30.08)and(72.32±25.46)ng·mL^(-1);t_(max) were 1.12,1.25 h;t_(1/2) were(14.02±7.40),(13.75±6.88)h;AUC_(0-t) were(530.93±221.48),(514.81±215.49)h·ng·mL^(-1);AUC_(0-∞) were(565.54±227.79),(514.81±215.49)h·ng·mL^(-1).The main pharmacokinetic parameters of total ezetimibe in plasma of test drug and reference drug after a single meal:C_(max) were(109.78±49.31),(112.33±40.73)ng·mL^(-1);t_(max) were 2.00,1.50 h;t_(1/2) were(15.50±8.76),(13.36±6.61)h;AUC_(0-t) were(627.51±267.46)and(565.57±188.63)h·ng·mL^(-1);AUC_(0-∞) were(683.91±316.10),(616.88±218.22)h·ng·mL^(-1).The main pharmacokinetic parameters C_(max),AUC_(0-t) and AUC_(0-∞)of the two drugs were analyzed by variance analysis after logarithmic transformation.The total ezetimibe under fasting state with 90%confidence interval were 88.90%-103.31%,97.84%-109.29%and 96.66%-109.94%;total ezetimibe in postprandial state were 84.79%-103.87%,102.71%-112.92%and 103.35%-115.71%.Conclusion The main pharmacokinetic parameters of the two ezetimibes are similar under fasted and fed conditions,and they are bioequivalent.

关 键 词:依折麦布 中国健康受试者 药代动力学 生物等效性 

分 类 号:R972.6[医药卫生—药品]

 

参考文献:

正在载入数据...

 

二级参考文献:

正在载入数据...

 

耦合文献:

正在载入数据...

 

引证文献:

正在载入数据...

 

二级引证文献:

正在载入数据...

 

同被引文献:

正在载入数据...

 

相关期刊文献:

正在载入数据...

相关的主题
相关的作者对象
相关的机构对象