目的 研究依托考昔片在中国健康受试者中的药代动力学特征,评价受试制剂和参比制剂的生物等效性及安全性.方法 采用随机、开放、单剂量、两制剂、两周期、交叉试验设计,空腹组和餐后组分别入组28例健康受试者,受试者单次口服依托考昔片受试制剂或参比制剂60 mg.用液相色谱-质谱联用(LC-MS/MS)法测定血浆中依托考昔的浓度,用WinNonlin 8.2软件计算药代动力学参数,并进行生物等效性及安全性评价.结果 空腹试验受试制剂与参比制剂的依托考昔Cmax分别为(1 176.96±287.95)和(1 164.93±189.65)ng·mL-1,AUC0-t分别为(18 651.95±6 100.27)和(19 241.39±6 107.48)ng·h·mL-1,AUC0-∞ 分别为(19 939.15±7 553.27)和(20 536.31±7 223.40)ng·h·mL-1.餐后试验受试制剂与参比制剂的依托考昔Cmax分别为(913.50±184.72)和(878.59±164.35)ng·mL-1,AUC0-t 分别为(19 085.22±5 155.01)和(18 669.54±4 508.21)ng·h·mL-1,AUC0-∞ 分别为(20 103.77±5 567.02)和(19 528.05±4 989.74)ng·h·mL-1.空腹组和餐后组受试制剂与参比制剂的Cmax、AUC0-t、AUC0-∞的几何均值比值的90％置信区间均落在80.00％～125.00％.空腹组和餐后组不良事件发生率分别为28.57％和21.43％.结论 中国受试者在空腹及餐后状态下,单次口服受试与参比依托考昔片均具生物等效性,且安全性良好.
Objective To study the pharmacokinetic characteristics of etoricoxib tablets in healthy Chinese subjects and to evaluate the bioequivalence and safety of the test and reference formulations.Methods In a randomised,single-dose,two-period,two-sequence crossover trial,28 healthy subjects were enrolled under the fasting and fed conditions,respectively,who received a single oral dose of 60 mg of etoricoxib tablets in the test or reference formulation.The concentration of etoricoxib in plasma was detected by LC-MS/MS,and the main pharmacokinetic parameters were calculated to evaluate bioequivalence and using WinNonlin 8.2 software.Results The main pharmacokinetic parameters of the test and reference preparations were as follows:The fasting condition Cmax of etoricoxib were(1 176.96±287.95)and(1 164.93±189.65)ng·mL-1;AUC0-t were(18 651.95±6 100.27)and(19 241.39±6 107.48)ng·h·mL-1;and AUC0-∞ were(19 939.15±7 553.27)and(20 536.31±7 223.40)ng·h·mL-1.The fed condition Cmax of etoricoxib were(913.50±184.72)and(878.59±164.35)ng·mL-1;and AUC0-t were(19 085.22±5 155.01)and(18 669.54±4 508.21)ng·h·mL-1;AUC0-∞ were(20 103.77±5 567.02)and(19 528.05±4 989.74)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters in the fasting and fed conditions fell between 80.00％and 125.00％.The incidence of adverse events in the fasting and fed conditions were 28.57％and 21.43％,respectively.Conclusion Two kinds of etoricoxib tablets are bioequivalent,and have similar safety in healthy Chinese subjects.
焦珍珍;许莉;刘曼;胡天泽;宋丹;王晓娟;赵志晶;刘会臣
中国医学科学院阜外医院、国家心血管病中心、国家心血管疾病临床医学研究中心Ⅰ期临床试验病房、国家卫生健康委员会心血管药物临床研究重点实验室,北京 100037
药学
依托考昔片;健康受试者;生物等效性;药代动力学;液相色谱-串联质谱法
etoricoxib tablets;healthy subject;bioequivalence;pharmacokinetics;liquid chromatography-tandem mass spectrometry(LC-MS/MS)
《中国临床药理学杂志》 2024 (005)
718-722 / 5
10.13699/j.cnki.1001-6821.2024.05.018
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