尼美舒利分散片在中国健康受试者中的生物等效性研究  

Bioequivalence study of nimesulide dispersible tablets in Chinese healthy subjects

作　　者：林柏炀 胡荣 张望刚 严静[3] LIN Bo-yang;HU Rong;ZHANG Wang-gang;YAN Jing(Graduate School,Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang Province,China;Phase I Clinical Trial Laboratory,Zhejiang Hospital,Hangzhou 310030,Zhejiang Province,China;Department of Critical Care Medicine,Zhejiang Hospital,Hangzhou 310030,Zhejiang Province,China;Nanchang Feihong Pharmaceutical Co.,Ltd,Nanchang 330096,Jiangxi Province,China)

机构地区：[1]浙江中医药大学研究生院,浙江杭州310053 [2]浙江医院Ⅰ期临床试验研究室,浙江杭州310030 [3]浙江医院重症医学科,浙江杭州310030 [4]南昌市飞弘药业有限公司,江西南昌330096

出　　处：《中国临床药理学杂志》2024年第21期3142-3146,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的比较尼美舒利分散片(受试制剂)和尼美舒利片(参比制剂)两制剂在中国健康受试者中的药代动力学参数,评价2种制剂的生物等效性。方法本试验用单中心、随机、开放、两制剂、两周期、双交叉的试验设计,纳入空腹组和餐后组各28例健康受试者,每周期单次口服尼美舒利受试制剂或参比制剂0.1 g,血液采集后,用液相色谱-串联质谱(LC-MS/MS)法测定人血浆中尼美舒利含量,计算药代动力学参数并进行生物等效性评价。结果在空腹组中,尼美舒利受试制剂和参比制剂主要药代动力学参数:C_(max)分别为(6262.14±1213.98)和(6625.36±1230.09)ng·mL^(-1),AUC_(0-t)分别为(4.48×10^(4)±1.66×10^(4))和(4.50×10^(4)±1.53×10^(4))h·ng·mL^(-1),AUC_(0-∞)分别为(4.60×10^(4)±1.83×10^(4))和(4.62×10^(4)±1.68×10^(4))h·ng·mL^(-1)。在餐后组中,尼美舒利受试制剂和参比制剂主要药代动力学参数:C_(max)分别为(6934.29±1371.00)和(6551.85±1383.91)ng·mL^(-1),AUC_(0-t)分别为(4.43×10^(4)±1.52×10^(4))和(4.50×10^(4)±1.47×10^(4))h·ng·mL^(-1),AUC_(0-∞)分别为(4.56×10^(4)±1.67×10^(4))和(4.64×10^(4)±1.60×10^(4))h·ng·mL^(-1)。在空腹组和餐后组中,受试制剂和参比制剂C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值比值的90%置信区间均落在80.00%~125.00%。空腹和餐后试验的不良事件发生率均为25.00%(7例/28例)。结论受试制剂尼美舒利分散片和参比制剂尼美舒利片在中国健康受试者体内具有生物等效性。Objective To compare the pharmacokinetic parameters of nimesulide dispersible tablets(test preparation)and nimesulide tablets(reference preparation)in Chinese healthy subjects and to evaluate the bioequivalence of two formulations.Methods This trial used a single-centre,randomised,open,two-preparation,two-cycle,two-way crossover experimental design.28 subjects were enrolled under fasting and fed conditions,who received a single oral dose of 0.1 g of nimesulide in the test or reference formulation each cycle.Plasma nimesulide concentration was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),calculation of pharmacokinetic parameters and bioequivalence evaluation.Results In fasting group,main pharmacokinetic parameters of the subject and reference formulations of nimesulide:C_(max)were(6262.14±1213.98)and(6625.36±1230.09)ng·mL^(-1),AUC_(0-t)were(4.48×10^(4)±1.66×10^(4))and(4.50×10^(4)±1.53×10^(4))h·ng·mL^(-1),AUC_(0-∞)were(4.60×10^(4)±1.83×10^(4))and(4.62×10^(4)±1.68×10^(4))h·ng·mL^(-1).In fed group,main pharmacokinetic parameters of the subject and reference formulations of nimesulide:C_(max)were(6934.29±1371.00)and(6551.85±1383.91)ng·mL^(-1),AUC_(0-t)were(4.43×10^(4)±1.52×10^(4))and(4.50×10^(4)±1.47×10^(4))h·ng·mL-1,AUC_(0-∞)were(4.56×10^(4)±1.67×10^(4))and(4.64×10^(4)±1.60×10^(4))h·ng·mL^(-1).The 90%confidence intervals for the geometric means of C_(max),AUC_(0-t),AUC_(0-∞)for reference and test preparations in the fasting and fed groups were in the range of 80.00%to 125.00%.The incidence of adverse events in both fasting and fed trials was 25.00%(7 cases/28 cases).Conclusion Nimesulide dispersible tablets were bioequivalent to the reference formulation nimesulide tablets in Chinese healthy subjects when taken under both fasting and fed conditions.

关 键 词：尼美舒利分散片 生物等效性 安全性评价 液相色谱-串联质谱法 

分 类 号：R971.1[医药卫生—药品]