替米沙坦片在中国健康受试者的生物等效性研究
Bioequivalence study of telmisartan tablets in Chinese healthy subjects
孙成 1张燕 1房红霞 1陈桂英 2章晓娟 2孙洪勋 3姜彬1
作者信息
- 1. 淄博万杰肿瘤医院Ⅰ期临床试验研究室,山东淄博 255213
- 2. 武汉宏韧生物医药股份有限公司,湖北武汉 430000
- 3. 淄博万杰制药有限公司,山东淄博 255200
- 折叠
摘要
目的 评价替米沙坦片(80 mg)受试制剂与参比制剂在中国健康受试者中的生物等效性.方法 采用单中心、随机、开放、两制剂、单次给药、餐后三周期三序列部分重复交叉和空腹四周期两序列完全重复交叉的生物等效性试验设计.餐后和空腹试验分别入组33和32例健康受试者,每周期分别单次口服受试制剂或参比制剂80 mg,用液相色谱-串联质谱法测定血浆中替米沙坦的浓度,用WinNonlin 8.3计算药代动力学参数,并用SAS 9.4进行统计分析.结果 空腹条件下口服替米沙坦片受试制剂或参比制剂后的主要药代动力学参数:Cma、分别为(556.10±456.06)和(580.99±533.50)ng·mL-1,AUC0-t 分别为(3 475.15±3 785.16)和(3 450.54±3 681.02)ng·mL-1·h,AUC0-∞ 分别为(3 214.06±2 272.06)和(3 194.84±2 187.45)ng·mL-1·h,2 种制剂 Cmax、AUC0-t和AUC0-∞几何均值比值及其90％置信区间,均落在80.00％～125.00％;餐后条件下口服替米沙坦片受试制剂或参比制剂后的主要药代动力学参数:Cmax分别为(299.26±124.72)和(291.29±126.34)ng·mL-1,AUC0-t分别为(3 682.24±2 799.72)和(3 636.71±2 158.42)ng·mL-1·h,AUC0-∞ 分别为(3 544.53±1 553.06)和(3 969.38±2 528.22)ng·mL-1·h,2 种制剂 Cmax、AUC0-t和AUC0-∞几何均值比值及其90％置信区间,均落在80.00％～125.00％.结论 空腹和餐后条件下,替米沙坦片受试和参比制剂在中国健康受试者中具有生物等效性.
Abstract
Objective To evaluation the bioequivalence of telmisartan tablets(80 mg)between test formulation and reference formulation in Chinese healthy subjects.Methods A single-center,randomized,open-label,two-preparations,single administration,partial repeat crossover of three sequences in three postprandial cycles and complete repeat crossover of two sequences in four fasting cycles,bioequivalence test was designed.Chinese healthy subjects were included in the bioequivalence trial,with 33 randomly assigned to the postprandial group and 32 randomly assigned to the fasting group.In each period,blood samples was collected before and after administration.The plasma concentration of the drug was determined by LC-MS/MS,using WinNonlin version 8.3 calculate the pharmacokinetic parameters and perform a statistical analysis using SAS version 9.4.Results The main pharmacokinetic parameters of telmisartan tablets after oral administration of test or reference were as follows.Fasting group Cmax were(556.10±456.06)and(580.99±533.50)ng·mL-1;AUC0-t were(3 475.15±3 785.16)and(3 450.54±3 681.02)ng·mL-1·h;AUC0-∞ were(3 214.06±2 272.06)and(3 194.84±2 187.45)ng·mL-1·h.The 90％confidence intervals of the geometric mean ratio of Cmax,AUC0-t,AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).Postprandial group Cmax were(299.26±124.72)and(291.29±126.34)ng·mL-1;AUC0-t were(3 682.24±2 799.72)and(3 636.71±2 158.42)ng·mL-1·h;AUC0-were(3 544.53±1 553.06)and(3 969.38±2 528.22)ng·mL-1·h.The 90％confidence intervals of the geometric mean ratio of Cmax,AUC0-t,AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).Conclusion Under fasting and fed conditions,two kinds of telmisartan tablets are bioequivalent in Chinese healthy subjects.
关键词
替米沙坦片/生物等效性/药代动力学参数Key words
telmisartan tablets/bioequivalence/pharmacokinetic parameters引用本文复制引用
基金项目
淄博万杰制药有限公司-南京迈迪信泽医药科技开发有限公司委托研发课题()
出版年
2024
国家科技期刊平台
NSTL
维普
万方数据