孟鲁司特钠咀嚼片在健康人体内的生物等效性  

BIOEQUIVALENCE OF MONTELUKAST SODIUM CHEWABLE TABLETS IN HEALTHY VOLUNTEERS

作　　者：张小蕾[1] 王晨静[2] 李欣[2] 柳艳平[2] 高华[1] 曹玉[2] ZHANG Xiaolei;WANG Chenjing;LI Xin;LIU Yanping;GAO Hua;CAO Yu(School of Pharmacy,Qingdao University,Qingdao 266021,China)

机构地区：[1]青岛大学药学院,山东青岛266021 [2]青岛大学附属医院Ⅰ期临床研究中心,山东青岛266021

出　　处：《青岛大学学报（医学版）》2022年第2期269-273,共5页Journal of Qingdao University(Medical Sciences)

基　　金：国家重大科技专项资助项目(2020ZX09201-018)。

摘　　要：目的评估空腹状态下孟鲁司特钠咀嚼片在人体内的生物等效性。方法试验采用随机、交叉、单剂量、两周期、两序列设计。入组的24例健康受试者在空腹状态下口服孟鲁司特钠咀嚼片受试制剂或参比制剂5mg,用高效液相色谱-质谱联用法测定血浆中的药物浓度,用WinNonlin􀆿7.0软件按非房室模型进行药代动力学参数的计算,并采用SAS9.4统计软件分析两种制剂的生物等效性。结果空腹单次给药后,孟鲁司特钠主要药动学参数如下:受试制剂、参比制剂的最大血药浓度(C_(max))分别为(247.83±65.49)和(277.08±56.09)μg/L;达峰时间(T_(max))分别为(3.15±1.40)和(2.79±0.94)h;半衰期(t_(1/2))分别为(5.02±0.60)和(5.07±0.59)h;从0时到最后计算时间点浓度-时间曲线下面积(AUC_(0-t))分别为(1862.74±409.99)和(1937.62±436.24)μg·h/L;从0时到无限时间浓度-时间曲线下面积(AUC_(0-∞))分别为(1939.89±442.26)和(2012.45±480.69)μg·h/L。受试制剂与参比制剂的C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比的90%置信区间均在80.00%~125.00%之间。结论在空腹状态下,孟鲁司特钠咀嚼片受试制剂与参比制剂具有生物等效性。Objective To evaluate the bioequivalence of montelukast sodium chewable tablets in fasting volunteers. Methods A randomized crossover single dose design was adopted with two phases and two sequences. The 24 healthy volunteers enrolled were orally administered 5 mg of montelukast sodium chewable tablets or reference formulation. Drug concentration in plasma was determined with high-performance liquid chromatography-mass spectrometry(HPLC-MS). Pharmacokinetic parameters were calculated using non-compartmental modeling in WinNonlin;7.0 software. The bioequivalence of both formulations was evaluated using SAS 9.4 software. Results After a single oral dose in fasting state, the pharmacokinetic parameters of montelukast sodium chewable tablets versus reference formulation were as follows: maximum plasma concentration(C_(max)) was(247.83±65.49) and(277.08±56.09) μg/L;time to maximum plasma concentration(T_(max)) was(3.15±1.40) and(2.79±0.94) h;half-life(t_(max)) was(5.02±0.60) and(5.07±0.59) h;the area under the concentration-time curve from 0 to the last measurable concentration(AUC_(0-t)) was(1 862.74±409.99) and(1 937.62±436.24) μg·h/L;the area under the concentration-time curve extrapolated to infinity(AUC_(0-∞)) was(1 939.89±442.26) and(2 012.45±480.69) μg·h/L. The 90% confidence intervals of geometric mean ratios of C_(max), AUC_(0-t) and AUC_(0-∞)of both formulations were 80.00%-125.00%. ConclusionMontelukast sodium chewable tablets and reference formulation are bioequivalent in fasting healthy volunteers.

关 键 词：孟鲁司特钠 白三烯拮抗剂 色谱法 液相 质谱分析法 药代动力学 治疗等效 

分 类 号：R969.1[医药卫生—药理学]