硫酸氨基葡萄糖胶囊的餐后人体生物等效性研究  

Study on postprandial bioequivalence of glucosamine sulfate capsules in healthy volunteers

作　　者：荆珊[1] 王欣 杨克旭[1] 刘文芳[1] 李静[1] 谭莉[1] 所伟[1] 鲁春艳[1] 林阳[1] Jing Shan;Wang Xin;Yang Kexu;Liu Wenfang;Li Jing;Tan Li;Suo Wei;Lu Chunyan;Lin Yang(Clinical Pharmacology Centre,Beijing Anzhen Hospital,Capital Medical University,Beijing,100029,China;Clinical Pharmacology Department,Zhejiang Hisun Pharmaceutical Co.,Ltd,Zhejiang Province,Taizhou 318000,China)

机构地区：[1]首都医科大学附属北京安贞医院临床药理中心,北京100029 [2]浙江海正药业股份有限公司临床药理部,台州318000

出　　处：《药物不良反应杂志》2021年第3期113-119,共7页Adverse Drug Reactions Journal

基　　金：“重大新药创制”科技重大专项(2017XZ09304017)。

摘　　要：目的评价国产与原研硫酸氨基葡萄糖胶囊的餐后人体生物等效性。方法试验设计为单中心、随机、开放、单剂量、两制剂、三序列、三周期部分重复的交叉设计,试验药物为国产硫酸氨基葡萄糖胶囊伊索佳(受试制剂)和原研硫酸氨基葡萄糖胶囊维固力(参比制剂)。将健康受试者随机分为3组,每组均服药3个周期,但服用受试制剂(T)和参比制剂(R)的顺序不同,分别为TRR、RTR、RRT组。受试者分别在试验第1、4、7天进餐后30 min时口服试验药物。每次服药前1天晚餐后1~2 h(基线1)、服药前60 min内(基线2)、服药后15、30、45、60、90、120、150 min和3、4、5、6、8、10、14、16 h采集受试者外周静脉血各4 ml,离心后取血浆冻存。应用液相色谱-串联质谱法测定血浆样品中氨基葡萄糖浓度,计算血药浓度-时间曲线下面积[AUC,包括从0时至最后一个浓度可准确测定的样品采集时间t的AUC(AUC_(0-t))和从0时至无限时间(∞)的AUC(AUC_(0-∞))]和药峰浓度(Cmax)等主要药动学参数。由于氨基葡萄糖为人体内源性物质,采用减去服药前基线值(基线1和基线2的平均值)的方法对测得的氨基葡萄糖血药浓度进行校正。受试制剂与参比制剂AUC_(0-t)、AUC_(0-∞)和Cmax的几何均数比值(GMR)及其90%置信区间(CI)落在0.800~1.250范围内为等效。结果纳入试验的健康受试者共30例,男性20例,女性10例;年龄(31±7)岁,范围18~45岁。TRR、RTR、RRT组各10例。TRR组1例于第1周期服药后脱落,余29例完成试验。受试制剂与参比制剂未经基线校正的AUC_(0-t)、AUC_(0-∞)、Cmax的GMR(90%CI)分别为0.985(0.941~1.031)、1.014(0.961~1.070)和0.937(0.827~1.062),经基线校正的AUC_(0-t)、AUC_(0-∞)、Cmax的GMR(90%CI)分别为0.977(0.923~1.035)、0.976(0.922~1.032)和0.932(0.817~1.063),均落在等效范围内(0.800~1.250)。试验期间3组受试者均未发生与试验药物相关的不良事件。结论国产与原研硫酸Objective To evaluate the postprandial bioequivalence of domestic and original glucosamine sulfate capsules in Chinese healthy volunteers.Methods The trial was a single-center,randomized,open-label,single-dose,2-preparation,3-sequence,3-period,partially repeated crossover design.The trialed drugs were domestic glucosamine sulfate capsules Yisuojia(test preparation)and original glucosamine sulfate capsules Viartril-(reference preparation).Healthy subjects were randomly divided into 3 groups,each group took medicine in 3 periods,but the order of taking test preparation(T)and reference preparation(R)was different,which were TRR,RTR and RRT groups.The healthy volunteers in the TRR,RTR,and RRT groups received the trialed drugs orally 30-minutes after diet supply on day 1,4,and 7,respectively.Peripheral venous blood samples 4-ml were collected at 1-2 hours after dinner the day before medication(baseline 1),within 60-minutes before medication(baseline 2),and 15,30,45,60,90,120,and 150-minutes and 3,4,5,6,8,10,14,and 16-hours after medication,respectively.Plasma was collected after centrifugation,frozen,and stored.Liquid chromatography-tandem mass spectrometry was used for the determination of glucosamine concentrations in plasma samples and main pharmacokinetic parameters such as the area under the concentration-time curve(AUC),including areas from time zero(pre-dose)to the last measurable concentration(AUC_(0-t))and extrapolated to infinite time(AUC_(0-∞)),and peak concentration(Cmax)were calculated.Because glucosamine was an endogenous substance in humans,the measured blood concentration of glucosamine was corrected by subtracting the baseline value before medication(the average of baseline 1 and baseline 2).The test and reference preparations were equivalent when the geometric mean ratios(GMR)and their 90%confidence intervals(CI)for AUC_(0-t),AUC_(0-∞),and Cmax all ranged from 0.800 to 1.250.Results A total of 30-healthy volunteers were enrolled in the study,including 20 males and 10 females,aged(31±7)years with

关 键 词：骨关节炎 临床试验 硫酸氨基葡萄糖 

分 类 号：R684.3[医药卫生—骨科学]