艾司西酞普兰片在中国健康受试者体内的生物等效性研究  

Bioequivalence of escitalopram tablets in Chinese healthy Subjects

作　　者：孙玲玲 刘剑锋[2] 伊金玲 柳云玲 林游游 熊文刚 罗茜 钟平 SUN Ling-ling;LIU Jian-feng;YI Jin-ling;LIU Yun-ling;LIN You-you;XIONG Wen-gang;LUO Xi;ZHONG Ping(Department of Intensive Care Unit,The First Affliated Hospital of Xiamen University,Xiamen 361003,Fujian Province,China;BE/Phase I Clinical Trial Center,The First Affliated Hospital of Xiamen University,Xiamen 361003,Fujian Province,China;AccuBE Pharma Tech Co.Ltd,Xiamen 361026,Fujian Province,China)

机构地区：[1]厦门大学附属第一医院重症医学科,福建厦门361003 [2]厦门大学附属第一医院BE/Ⅰ期临床试验中心,福建厦门361003 [3]莱必宜科技(厦门)有限公司,福建厦门361026

出　　处：《中国临床药理学杂志》2023年第6期859-863,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究艾司西酞普兰在空腹和餐后条件下中国健康受试者体内的生物等效性。方法用单剂量、随机、开放、两周期、两序列、双交叉试验设计。空腹和餐后试验各纳入26例健康受试者,每周期空腹或餐后单次口服艾司西酞普兰片受试制剂或参比制剂10 mg。用HPLC-MS/MS法测定艾司西酞普兰血药浓度,用WinNonlin 8.0计算艾司西酞普兰药代动力学参数,评价受试制剂和参比制剂的生物等效性。结果空腹试验中艾司西酞普兰受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(13.80±2.71)和(14.10±3.16)ng·mL^(-1);AUC_(0-t)分别为(450.52±178.35)和(428.26±153.18)ng·mL^(-1)·h;AUC_(0-∞)分别为(491.35±219.49)和(459.47±182.20)ng·mL^(-1)·h。餐后试验中艾司西酞普兰受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(15.10±2.68)和(14.00±2.59)ng·mL^(-1);AUC_(0-t)分别为(489.40±155.25)和(458.61±107.06)ng·mL^(-1)·h;AUC_(0-∞)分别为(527.82±205.84)和(486.83±131.00)ng·mL^(-1)·h。空腹和餐后试验(受试制剂/参比制剂)的C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比90%置信区间均在80.00%~125.00%内。空腹和餐后试验过程中不良事件发生率分别为57.69%(15例/26例)和38.46%(10例/26例),且试验过程均无严重不良事件及非预期不良事件发生。结论空腹和餐后给药条件下,2种艾司西酞普兰片制剂具有生物等效性,且安全性良好。Objective To study the bioequivalence of escitalopram in healthy Chinese subjects under fasting and fed conditions.Methods A single oral dose of 10 mg of escitalopram oxalate tablet was administrated with test preparation(T)and reference preparation(R)in a randomized,open-label,two-period,two-sequence crossover study.52 subjects were enrolled for fasting condition(n=26)and fed condition(n=26).The concentration of escitalopram in the plasma of healthy subjects was determined by HPLC-MS/MS,using WinNonlin 8.0 to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the test and the reference escitalopram oxalate tablets.Results The main pharmacokinetic parameters of a single oral escitalopram oxalate tablet under fasting condition for T and R were as follows:C_(max)were(13.80±2.71)and(14.10±3.16)ng·mL^(-1);AUC_(0-t)were(450.52±178.35)and(428.26±153.18)ng·mL^(-1)·h;AUC_(0-∞)were(491.35±219.49)and(459.47±182.20)ng·mL^(-1)·h.The main pharmacokinetic parameters of a single oral escitalopram oxalate tablet under fed conditions for T and R were as follows:C_(max)were(15.10±2.68)and(14.00±2.59)ng·mL-;AUC_(0-t)were(489.40±155.25)and(458.61±107.06)ng·mL^(-1)·h;AUC_(0-∞)were(527.82±205.84)and(486.83±131.00)ng·mL^(-1)·h.The90%CIs for the geometric mean ratios of C_(max),AUC0-1and AUC_(0-∞)of T and R under fasting and fed condition were within the 80.00%-125.00%interval respectively.Under fasting and fed conditions,the adverse event incidence rate were 57.69%(15 cases/26 cases)and 38.46%(10 cases/26 cases),and there were no serious adverse events and unexpected adverse events during the trial.Conclusion Both of the two kinds of escitalopram oxalate tablets are bioequivalent and safe under fasting and fed conditions.

关 键 词：艾司西酞普兰 液相串联质谱法 药代动力学 生物等效性 

分 类 号：R971.4[医药卫生—药品]