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

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.