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 Chinese healthy volunteers

作　　者：陈元璐 谢朋飞[1] 崔宏娣 龙辉[1] 周燕 黄启山 杨鹏 张永东[1] CHEN Yuan-lu;XIE Peng-fei;CUI Hong-di;LONG Hui;ZHOU Yan;HUANG Qi-shan;YANG Peng;ZHANG Yong-dong(PhaseⅠClinical Centre,Chenzhou First People's Hospital,Chenzhou Hunan 423000;Anhui Wanbang Pharmaceutical Technology Co.,Ltd.,Hefei 230000;Anhui Menjie Technology Development Co.,Ltd,Hefei 230000)

机构地区：[1]郴州市第一人民医院Ⅰ期临床研究室,湖南郴州423000 [2]安徽万邦医药科技股份有限公司,合肥230000 [3]安徽门捷科技发展有限公司,合肥230000

出　　处：《中南药学》2022年第3期494-498,共5页Central South Pharmacy

基　　金：国家卫健委重大新药创制科技重大专项课题(No.2020ZX09201010);郴州市科技发展计划项目(No.yfzx201912);郴州市第一人民医院院级科研项目(No.N2019-025)。

摘　　要：目的评价两种孟鲁司特钠咀嚼片在中国成年健康受试者中的生物等效性。方法空腹和餐后各28例健康受试者,采用单中心、单剂量、随机、开放、双周期、双交叉试验设计,受试者口服单剂量孟鲁司特钠咀嚼片受试制剂(T)和参比制剂(R)5 mg。采用液相色谱串联质谱(LC-MS/MS)法测定血浆中孟鲁司特的浓度,采用WinNonlin 7.0程序数据统计软件按非房室模型计算药动学参数,并进行生物等效性评价。结果空腹单剂量给药孟鲁司特T和R的主要药动学参数:t_(max)分别为(2.69±0.90)、(3.41±1.23)h;C_(max)分别为(353.84±72.43)、(328.07±71.16)ng·m^(L-1);AUC0~t分别为(2241.99±467.78)、(2273.08±486.16)h·ng·m^(L-1);AUC_(0~∞)分别为(2271.07±465.53)、(2305.09±485.04)h·ng·m^(L-1);t1/2分别为(5.28±0.54)、(5.18±0.50)h,以AUC0~48 h计算T的平均相对生物利用度为(99.28±10.73)%;餐后单剂量给药条件下孟鲁司特T和R的主要药动学参数:t_(max)分别为(3.98±1.20)、(3.84±1.28)h;C_(max)分别为(270.49±43.64)、(279.98±53.50)ng·m^(L-1);AUC0~t分别为(2292.33±536.61)、(2326.34±579.80)h·ng·m^(L-1);AUC_(0~∞)分别为(2322.20±539.93)、(2361.58±583.75)h·ng·m^(L-1);t1/2分别为(4.94±0.60)、(4.94±0.61)h,以AUC0~t计算T的平均相对生物利用度为(99.12±7.49)%。空腹单次服用孟鲁司特钠咀嚼片T和R的C_(max)、AUC0~t、AUC_(0~∞)的几何均值比90%置信区间分别为101.88%~114.57%、95.72%~101.88%、95.69%~101.69%。餐后T和R的C_(max)、AUC0~t、AUC_(0~∞)的几何均值比90%置信区间分别为91.34%~103.30%、96.46%~101.30%、96.33%~101.03%。结论两种孟鲁司特钠咀嚼片在中国健康受试者体内具有生物等效性。Objective To evaluate the bioequivalence of two montelukast sodium chewable tablets in Chinese healthy volunteers.Methods Totally 28 healthy volunteers and 28 healthy volunteers were recruited in fasting and fed conditions respectively.Single-center,single-dose,open,randomized,double cycle and self-crossover design was used.A single oral dose of montelukast sodium chewable tablets included test preparation(T)and reference preparation(R)5 mg.The concentration of montelukast in the plasma was determined by LC-MS/MS method.The pharmacokineric parameters were calculated and the bioequivalence was determined by non-compartment model of WinNonLin 7.0.Results The main pharmacokinetic parameters of a single oral montelukast sodium chewable tablets under fasting condition for T and R were:t_(max) was(2.69±0.90)and(3.41±1.23)h;C_(max) was(353.84±72.43)and(328.07±71.16)ng·mL^(-1);AUC0~t was(2241.99±467.78)and(2273.08±486.16)h·ng·mL^(-1);AUC_(0~∞)was(2271.07±465.53)and(2305.09±485.04)h·ng·m^(L-1);t1/2 was(5.28±0.54)and(5.18±0.50)h,respectively.The relative bioavailability of montelukast T to R was(99.28±10.73)%with AUC0~48 h.The main pharmacokinetic parameters of a single oral montelukast sodium chewable tablets under fed condition for T and R were calculated:t_(max) was(3.98±1.20)and(3.84±1.28)h,C_(max) was(270.49±43.64)and(279.98±53.50)ng·m^(L-1),AUC0~t was(2292.33±536.61)and(2326.34±579.80)h·ng·m^(L-1),AUC_(0~∞)was(2322.20±539.93)and(2361.58±583.75)h·ng·m^(L-1),t1/2 was(4.94±0.60)and(4.94±0.61)h.The relative bioavailability of montelukast T to R was(99.12±7.49)%with AUC0~t.The 90%CI for the geometric mean ratios of C_(max),AUC0~t and AUC_(0~∞)of T and R under fasting condition was 101.88%-114.57%,95.72%-101.88%,and 95.69%-101.69%,respectively.The 90%CI for the geometric mean ratios of C_(max),AUC0~t and AUC_(0~∞)of T and R under fed condition was 91.34%-103.30%,96.46%-101.30%,and 96.33%-101.03%,respectively.Conclusion The two montelukast sodium chewable tablets are bioequivalent in

关 键 词：孟鲁司特钠咀嚼片 生物利用度 生物等效性 

分 类 号：R96[医药卫生—药理学]