阿立哌唑口腔崩解片在中国健康受试者中的生物等效性研究  

Bioequivalence study of aripiprazole orally disintegrating tablets in Chinese healthy subjects

作　　者：陈松[1] 谭云龙[1] 杨少杰[1] 顾兴丽 陈秀玉 王庆[1] 杨甫德[1] CHEN Song;TAN Yun-long;YANG Shao-jie;GU Xing-li;CHEN Xiu-yu;WANG Qing;YANG Fu-de(Institution of Drug Clinical Trial,Clinical Medical School,Peking University Huilongguan,Beijing Huilongguan Hospital,Beijing Huilongguan Hospital,Beijing 100096,China;Qilu Pharmaceutical,Jinan 250101,Shandong Province,China)

机构地区：[1]北京回龙观医院北京大学回龙观临床医学院药物临床试验机构,北京100096 [2]齐鲁制药有限公司,山东济南250101

出　　处：《中国临床药理学杂志》2022年第11期1237-1241,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价2种阿立哌唑口腔崩解片在中国健康受试者中空腹和餐后条件下单剂量给药的生物等效性,以及评估两制剂的安全性。方法采用单次给药、单中心、开放、随机、2周期、2序列、双交叉生物等效性试验设计,空腹和餐后条件下各纳入32例健康受试者,随机交叉单次口服受试制剂和参比制剂10 mg,用经验证的液相色谱-串联质谱(LC-MS/MS)法测定血浆中阿立哌唑的浓度。用SAS V9.3软件计算主要药代动力学参数C_(max)、AUC_(0-72)。将C_(max)、AUC_(0-72)经对数转换后,进行方差分析和90%置信区间分析。结果空腹组阿立哌唑口腔崩解片受试制剂和参比制剂的药代动力学参数如下:C_(max)分别为(51.92±16.18)和(51.27±13.78)ng·mL^(-1),AUC_(0-72)分别为(1771.12±399.05)和(1823.22±352.36)ng·h·mL^(-1),t_(max)中位数均为2.00 h,t_(1/2)分别为(84.39±38.82)和(80.47±25.22)h。餐后组阿立哌唑口腔崩解片受试制剂和参比制剂的药代动力学参数如下:C_(max)分别为(42.47±9.00)和(43.36±10.04)ng·mL^(-1),AUC_(0-72)分别为(1831.68±378.95)和(1831.58±358.77)ng·h·mL^(-1),t_(max)中位数均为4.50 h,t_(1/2)分别为(71.87±23.25)和(70.95±27.34)h。空腹组受试制剂和参比制剂C_(max)、AUC_(0-72)几何均值比的90%置信区间分别为91.86%~106.83%和92.04%~100.92%,餐后组受试制剂和参比制剂C_(max)、AUC_(0-72)几何均值比的90%置信区间分别为92.65%~105.08%和96.62%~102.92%。研究过程中无严重不良事件发生。结论在空腹及餐后条件下,中国健康受试者单次口服阿立哌唑口腔崩解片受试制剂与参比制剂具有生物等效性,并且安全性相似。Objective To evaluate the bioequivalence of the two aripiprazole orally disintegrating tablets and their safety in Chinese healthy subjects under fasting and fed conditions.Methods A single-site,open-label,randomized,single-dose,two periods,double-crossover design was conducted.Thirty-two healthy subjects were enrolled into the fasting group and fed group respectively,and received single oral dose 10 mg of test and reference aripiprazole orally disintegrating tablets.The concentrations of aripiprazole in plasma were determined by verified LC-MS/MS method.The pharmacokinetic parameters were calculated by SAS V9.3 software.Ln-transformed PK parameters of C_(max) and AUC_(0-72) will be analyzed using analysis of variance and 90%confidence intervals(CIs).Results In the fasting state,the pharmacokinetic parameters of test and reference product of aripiprazole orally disintegrating tablets were as follows:C_(max) were(51.92±16.18)and(51.27±13.78)ng·mL^(-1),AUC_(0-72) were(1771.12±399.05)and(1823.22±352.36)ng·h·mL^(-1),both median of t_(max) were 2.00 h,t_(1/2) were(84.39±38.82)and(80.47±25.22)h,respectively.In the fed state,the pharmacokinetic parameters of test and reference product of aripiprazole orally disintegrating tablets were as follows:C_(max) were(42.47±9.00)and(43.36±10.04)ng·mL^(-1),AUC_(0-72) were(1831.68±378.95)and(1831.58±358.77)ng·h·mL^(-1),both median of t_(max) were 4.50 h,t_(1/2) were(71.87±23.25)and(70.95±27.34)h,respectively.Under fasting condition,90%CIs of the test/reference product were 91.86%-106.83%for the C_(max),and 92.04%-100.92%for the AUC_(0-72).Under fed condition,90%CIs of the test/reference product for C_(max) and AUC_(0-72)were92.65%-105.08%and 96.62%-102.92%,respectively.No serious adverse events occurred during the study.Conclusion The test and reference product of aripiprazole orally disintegrating tablets were bioequivalent and safe under both fasting and fed conditions in Chinese healthy subjects.

关 键 词：阿立哌唑口腔崩解片 生物等效性 药代动力学 液相色谱-串联质谱法 

分 类 号：R971[医药卫生—药品]