孟鲁司特钠咀嚼片在中国健康受试者中的生物等效性研究  

Bioequivalence of montelukast sodium chewable tablets in healthy Chinese subjects

作　　者：华烨[1,2] 张海波 买买提居马·对先[1] 扈向润[1] 李颖[3] 毕吕存 杨雪 徐春来 谢伟娜 王林 徐继承 杨建华 HUA Ye;ZHANG Hai-bo;DUIXIAN Mai-mai-ti-ju-ma;HU Xiang-run;LI Ying;BI Lü-cun;YANG Xue;XU Chun-lai;XIE Wei-na;WANG Lin;XU Ji-cheng;YANG Jian-hua(Department of Pharmaceutical,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,Xinjiang Uygur Autonomous Region,China;Xinjiang Medical University,Urumqi 830000,Xinjiang Uygur Autonomous Region,China;Covance Medical R&D(Shanghai)Co.Ltd,Shanghai 200000,China;Yangtze River Pharmaceutical Group,Taizhou 225300,Jiangsu Province,China)

机构地区：[1]新疆医科大学第一附属医院药学部,新疆乌鲁木齐830000 [2]新疆医科大学,新疆乌鲁木齐830000 [3]科文斯医药研发(上海)有限公司,上海200000 [4]扬子江药业集团有限公司,江苏泰州225300

出　　处：《中国临床药理学杂志》2021年第10期1133-1137,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家科技重大专项重大新药创制基金资助项目(2020ZX09201-030);乌鲁木齐市科学技术计划基金资助项目(H171312002)。

摘　　要：目的评价2种孟鲁司特钠咀嚼片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、单剂量、双周期、双交叉试验设计,空腹和餐后条件下各入组24例健康受试者,随机交叉单次口服孟鲁司特钠咀嚼片受试制剂和参比制剂5 mg,用LC-MS/MS法测定血浆中孟鲁司特的浓度,用WinNonlin 7.0软件计算药代动力学参数,用SAS 9.4软件评价生物等效性。结果受试者口服孟鲁司特钠咀嚼片受试制剂与参比制剂5 mg后,主要药代动力学参数如下:空腹组Cmax分别为(311.91±56.82)和(297.92±69.30)ng·mL^(-1),AUC0-t分别为(1968.30±442.29)和(1940.38±458.19)ng·h·mL^(-1),AUC0-∞分别为(2047.60±480.74)和(2013.03±483.28)ng·h·mL^(-1);餐后组Cmax分别为(292.93±64.70)和(284.10±61.79)ng·mL^(-1),AUC0-t分别为(1851.69±374.26)和(1833.54±454.75)ng·h·mL^(-1),AUC0-∞分别为(1917.17±398.69)和(1897.29±489.54)ng·h·mL^(-1)。2种制剂的Cmax、AUC0-t和AUC0-∞经对数转换后90%置信区间空腹状态下分别为98.76%~113.22%,97.87%~105.98%和97.95%~106.22%;餐后状态下分别为96.78%~109.84%,96.84%~106.59%和96.75%~106.96%。结论无论是空腹还是餐后单次口服2种孟鲁司特钠咀嚼片在中国健康受试者体内均具有生物等效性。Objective To evaluate the bioequivalence of the two montelukast sodium chewable tablets in Chinese healthy subjects. Methods This was a single-center, randomized, open, single dose, two periods, double-crossover design. A total of 24 subjects in fasting state and 24 subjects in fed state were given single oral dose 5 mg of test and reference montelukast sodium chewable tablets. The concentrations of montelukast in plasma were determined by LC-MS/MS method. The pharmacokinetic parameters were calculated by WinNonlin 7.0 software, and the bioequivalence was evaluated by SAS 9.4 software. Results The main pharmacokinetics parameters of test and reference preparations were as follows: in fasting state, Cmax were(311.91±56.82) and(297.92±69.30) ng·mL^(-1),AUC0-t were(1968.30±442.29) and(1940.38±458.19) ng·h·mL^(-1),AUC0-∞ were(2047.60±480.74) and(2013.03±483.28) ng·h·mL^(-1);in fed state, Cmax were ( 292. 93 ± 64. 70) and( 284. 10 ± 61. 79) ng·mL^(-1),AUC0-twere( 1851. 69 ± 374. 26) and( 1833. 54 ± 454. 75)ng·h·mL^(-1),AUC0-∞were( 1917. 17 ± 398. 69) and( 1897. 29 ± 489. 54) ng·h·mL^(-1). The 90% CIs for Cmax,AUC0-tand AUC0-∞in fasting state were 98. 76%-113. 22%,97. 87%-105. 98% and 97. 95%-106. 22%;in fed state were 96. 78%-109. 84%,96. 84%-106. 59% and 96. 75%-106. 96%,respectively. Conclusion The exposures were equivalent between two montelukast sodium chewable tablets administered in fasting or fed state in Chinese healthy subjects.

关 键 词：孟鲁司特钠咀嚼片 生物等效性 药代动力学 空腹和餐后 液相色谱-串联质谱法 

分 类 号：R974[医药卫生—药品]