泊沙康唑肠溶片在健康受试者的生物等效性研究  

Bioequivalence study of posaconazole enteric-coated tablets in healthy subjects

作　　者：张永恒[1] 周铭 BHAVIN Patel 沈建人 李坤 ZHANG Yong-heng;ZHOU Ming;BHAVIN Patel;SHEN Jian-ren;LI Kun(Department of Pharmacy,The First Affiliated Hospital of Xinxiang Medical College,Weihui 453000,Henan Province,China;Department of Pharmacy,Wuhan Pulmonary Hospital,Wuhan 430000,Hubei Province,China;Cliantha Research Limited,Vadodara 390020,Gujarat,India;Sinotherapeutics Ina,Shanghai 200000,China)

机构地区：[1]新乡医学院第一附属医院药学部,河南卫辉453100 [2]武汉市肺科医院药剂科,湖北武汉430000 [3]Cliantha临床研究有限公司,巴罗达印度古吉拉特邦390020 [4]上海宣泰医药科技股份有限公司,上海200000

出　　处：《中国临床药理学杂志》2022年第7期699-702,707,共5页The Chinese Journal of Clinical Pharmacology

基　　金：上海市国资委企业技术创新和能级提升基金资助项目(2013033);上海市科技计划小巨人培育基金资助项目(1902HX83300)。

摘　　要：目的研究健康受试者中泊沙康唑肠溶片的药代动力学,评估国产受试制剂与原研参比制剂的生物等效性.方法用单中心、随机、开放、单剂量、两周期、两序列、双交叉、空腹或餐后给药试验设计,空腹组和餐后组分别入组44例和34例健康受试者口服泊沙康唑肠溶片受试制剂或参比制剂100 mg.用LC-MS/MS法测定血浆中泊沙康唑的浓度,用WinNonlin■8.0版计算药代动力学参数,SAS■9.4版对主要药代动力学参数进行了生物等效性分析评价.结果空腹试验受试制剂和参比制剂的泊沙康唑C_(max)分别为(174.28±71.34)和(169.41±63.43)ng·mL^(-1),AUC_(0-t)分别为(5972.47±2118.29)和(5685.16±2054.80)h·ng·mL^(-1),AUC_(0-∞)分别为(6222.48±2304.83)和(5912.98±2165.39)h·ng·mL^(-1).餐后试验受试制剂和参比制剂的泊沙康唑C_(max)分别为(439.08±100.88)和(440.52±110.73)ng·mL^(-1),AUC_(0-t)分别为(1.32×10^(4)±2928.30)和(1.32×10^(4)±2982.31)h·ng·mL^(-1)、AUC_(0-∞)分别为(1.37×10^(4)±3137.21)和(1.36×10^(4)±3191.62)h·ng·mL^(-1).空腹组和餐后组受试制剂/参比制剂的泊沙康唑主要药代动力学参数经对数转换后几何均值比(90%CI)均落在80.00%~125.00%.在试验过程中,空腹试验组和餐后试验组不良事件反应发生率分别为2.2%和0,未发生严重不良事件.结论2种泊沙康唑肠溶片在餐后和空腹给药条件下在印度健康受试者体内生物等效、安全.Objective To study pharmacokinetics and bioequivalence of two posaconazole enteric-coated tablets in healthy subjects.Methods The study is a single-center,randomized,open-labeled,single dose,two-period,two-sequence,crossover design.Forty-four and thirty-four subjects are received test or reference posaconazole enteric-coated tablets 100 mg under both fasted and fed conditions respectively.The concentrations of posaconazole in plasma were determined by LC-MS/MS method.The pharmacokinetic parameters were calculated by Win Nonlin■8.0 and the bioequivalence was analyzed and evaluated by SAS■9.4.Results The main pharmacokinetics parameters(C_(max),AUC_(0-t),AUC_(0-∞))of tested products and reference products under fasted state were as follows:(174.28±71.34)and(169.41±63.43)ng·m L^(-1);(5972.47±2118.29)and(5685.16±2054.80)h·ng·m L^(-1);(6222.48±2304.83)and(5912.98±2165.39)h·ng·m L^(-1).The main pharmacokinetics parameters(C_(max),AUC_(0-t),AUC_(0-∞))of tested products and reference products under fed state were as follows:(439.08±100.88)and(440.52±110.73)ng·m L^(-1),(1.32×10^(4)±2928.30)and(1.32×10^(4)±2982.31)h·ng·m L^(-1);(1.37×10^(4)±3137.21)and(1.36×10^(4)±3191.62)h·ng·m L^(-1).The geometric mean ratio(90%confidence interval)after logarithmic conversion for C_(max),AUC_(0-t),AUC_(0-∞)were between 80.00%and 125.00%in fasting and fed group.During the trial,the incidence of adverse events in fasting and fed groups was 2.2%and 0,and no serious adverse events occurred.Conclusions The two posaconazole enteric-coated tablets were bioequivalent and safe in healthy Indian subjects under fasted and fed condition.

关 键 词：泊沙康唑肠溶片 空腹及餐后 生物等效性 安全性 

分 类 号：R97[医药卫生—药品]