2种格列齐特片在中国健康人体的生物等效性研究  

Bioequivalence of gliclazide tablets in Chinese healthy volunteers

作　　者：侯振彦 颜苗[1,2] 蔡骅琳[1,2] 邓阳[1,2,3] 吴艳琴[1,2] 曹思思[1,2] 张毕奎[1,2] 

机构地区：[1]中南大学湘雅二医院药学部,长沙410011 [2]中南大学临床药学研究所,长沙410011 [3]湖南中医药大学药学院,长沙410028

出　　处：《中南药学》2017年第11期1524-1528,共5页Central South Pharmacy

摘　　要：目的研究2种格列齐特片在中国健康受试者的药动学和生物等效性。方法采用单中心、随机、自身交叉对照、双周期试验设计,24名健康志愿者(包括16名男性和8名女性)单剂量空腹给予80 mg(1片)格列齐特片受试制剂或参比制剂后,用高效液相色谱-串联质谱(HPLC-MS/MS)法测定血浆格列齐特浓度,计算药动学参数,进行生物等效性判定。结果格列齐特片受试制剂和参比制剂的主要药动学参数如下:tmax分别为(4.50±1.89)h和(4.21±1.61)h,Cmax分别为(5959.86±1251.32)ng·mL^(-1)和(6003.26±1357.84)ng·mL^(-1),AUC0~72分别为(100 251.84±42 195.63)ng·h·mL^(-1)和(102 778.12±46 622.56)ng·h·mL^(-1),AUC0~∞分别为(105 221.44±48 385.47)ng·h·mL^(-1)和(108 360.52±53 614.41)ng·h·mL^(-1),t1/2分别为(13.67±5.51)h和(14.05±6.16)h。受试制剂对参比制剂的相对生物利用度为(99.01±11.40)%。经对数转换后,受试制剂的Cmax、AUC0~72、AUC0~∞90%置信区间分别为95.11%~105.02%、86.33%~111.13%、86.89%~110.77%,均在参比制剂的80%~125%内。方差分析结果表明,受试制剂和参比制剂的主要药动学参数之间差异无统计学意义(P>0.05);tmax的配对Wilcoxon检验结果表明,2种药物的tmax差异无统计学意义(P>0.05);双单侧t检验结果表明,受试制剂与参比制剂为生物等效制剂。试验期间无任何不良事件发生。结论 2种格列齐特片具有生物等效性。Objective To determine the pharmacokinetics and bioequivalence of 2 gliclazide tablets in Chinese laealthy volunteers. Methods A single-center, randomized, cross-over, two way study design was used. Under fasting conditions, a single oral dose of the test or the reference gliclazide tablets was given to 24 subjects （16 males and 8 females）. The plasma concentrations of gliclazide were determined by a high performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were calculated. Results The main pharmacokinetic parameters of gliclzide in the test and the reference preparations were as follows： tmax was （4.50±1.89） h and （4.21±1.61） h; Cmax was （5959.86±1251.32） ng·mL-1 and （6003.26±1357.84） ng·mL^-l; AUCo_72 was （100 251.84±42 195.63） ng · h · mL - 1 and （102 778.12±46 622.56） ng· h · mL - 1; AUC0- was （105 221.44±48 385.47） ng.h·mL-1 and （108 360.52±53±614.41） ng·h·mL^-1; and t1/2 was （13.67±5.51） h and （14.05±6.16） h. The relative bioavailability was （99.01±11.40）%. After logarithmic transformation, the 90% confidence intervals of Cmax, AUC0-∞ and AUC0-∞ were 95.11% -- 105.02%, 86.33% -111.13% and 86.89% - 110.77%, respectively. No significant difference was found among the main pharmacokinetic parameters between the trial preparation and the reference preparation （P 〉 0.05） by ANOVA. No significant difference was found in tmax between the trial preparation and the reference preparation （P 〉 0.05） by non- parametric test. The two one-sided t-tests showed that the trial preparation and the reference preparation were bioequivalent. No adverse events were found or reported during the study. Conclusion The 2 gliclazide tablets are bioequivalent.

关 键 词：格列齐特 高效液相色谱.串联质谱法 药动学 生物等效性 

分 类 号：R96[医药卫生—药理学]