磷酸奥司他韦干糖浆在中国健康受试者中的生物等效性研究  

Bioequivalence study of oseltamivir phosphate dry syrup in Chinese healthy subjects

作　　者：刘娴 秦如斋[2] 成玘 陈学义 易德平 黄和意 谢志红[2] 叶丽卡[2] 段炼[2] LIU Xian;QIN Ru-zhai;CHENG Qi;CHEN Xue-yi;YI De-ping;HUANG He-yi;XIE Zhi-hong;YE Li-ka;DUAN Lian(TheSecond School of Clinical Medicine,Guangzhou Medical University,Guangzhou 510260,Guangdong Province,China;Phase I Clinical Trial Center,The Second Affiliated Hospital,Guangzhou Medical University,Guangzhou 510260,Guangdong Province,China;Beijing Scinovo Laboratories Ltd.,Bejing 100162,China;ZORUNPHARMA Co.,Ltd.,Guangzhou 510530,Guangdong Province,China)

机构地区：[1]广州医科大学第二临床学院,广东广州510260 [2]广州医科大学附属第二医院Ⅰ期临床试验中心,广东广州510260 [3]北京阳光德美医药科技有限公司,北京100162 [4]中润药业有限公司,广东广州510530

出　　处：《中国临床药理学杂志》2025年第5期706-711,共6页The Chinese Journal of Clinical Pharmacology

基　　金：广州市科技计划重点研发计划基金资助项目(202103000024);广东省医学科学技术研究基金资助项目(B2023146)。

摘　　要：目的研究磷酸奥司他韦干糖浆在中国健康受试者中的药代动力学特征,并评价受试制剂(T)和参比制剂(R)在空腹和餐后条件下的生物等效性及安全性。方法采用随机、开放、两制剂、两序列、两周期、双交叉的试验设计,空腹组和餐后组分别入组36例健康受试者,受试者单次口服磷酸奥司他韦干糖浆受试制剂或参比制剂2.5 g。用液相色谱-质谱(LC-MS/MS)法测定奥司他韦的血药浓度,用WinNonlin(8.2)软件计算药代动力学参数,并进行生物等效性及安全性评价。结果在空腹条件下,受试制剂与参比制剂的奥司他韦Cmax分别为(64.40±17.50)和(64.10±20.90)ng·mL^(-1),AUC0-t分别为(142.76±43.64)和(151.60±35.10)h·ng·mL^(-1),AUC0-∞分别为(147.67±37.60)和(153.05±35.30)h·ng·mL^(-1)。在餐后条件下,受试制剂与参比制剂的奥司他韦Cmax分别为(47.70±18.30)和(46.90±17.20)ng·mL^(-1),AUC0-t分别为(170.52±26.28)和(168.70±24.51)h·ng·mL^(-1),AUC0-∞分别为(173.08±26.50)和(171.30±24.59)h·ng·mL^(-1)。空腹组和餐后组受试制剂与参比制剂中奥司他韦的Cmax、AUC0-t和AUC0-∞的几何均值比值的90%置信区间均落在80.00%~125.00%。空腹组和餐后组药物不良反应发生率分别为27.78%和44.44%。结论中国健康受试者在空腹及餐后状态下,单次服用受试与参比磷酸奥司他韦干糖浆均具有生物等效性,且安全性良好。Objective To study the pharmacokinetic profile of oseltamivir phosphate dry syrup in Chinese healthy subjects and to evaluate the bioequivalence and safety of the test formulation(T)and the reference formulation(R)under fasting and fed conditions.Methods In a randomized,open,two-agent,two-sequence,two-cycle,double-crossover trial design,36 healthy subjects were enrolled in the fasting and fed groups,respectively,who received a single oral dose of2.5 g of oseltamivir phosphate dry syrup of either the T or R.The blood concentrations of oseltamivir were determined by liquid chromatographytandem mass spectrometry(LC-MS/MS),and the pharmacokinetic parameters were calculated by using the WinNonlin(8.2)software and evaluated for bioequivalence and safety.Results Under fasting conditions,theC_(max)of oseltamivir of the T and R were(64.40±17.50)and(64.10±20.90)ng·mL^(-1),AUC_(0-t)were(142.76±43.64)and(151.60±35.10)h·ng·mL^(-1),AUC_(0-∞)were(147.67±37.60)and(153.05±35.30)h·ng·mL^(-1),respectively.Under fed conditions,theC_(max)of oseltamivir of the T and R were(47.70±18.30)and(46.90±17.20)ng·mL^(-1),AUC_(0-t)were(170.52±26.28)and(168.70±24.51)h·ng·mL^(-1),AUC_(0-∞)were(173.08±26.50)and(171.30±24.59)h·ng·mL^(-1),respectively.The 90%confidence intervals for the geometric mean ratios of C_(max),AUC_(0-t)and AUC_(0-∞)for the T and R fell in the range of 80.00%to 125.00%for both the fasting and fed groups.Adverse drug reaction rates were 27.78%and 44.44%in the fasting and fed groups,respectively.Conclusion Two kinds of oseltamivir phosphate dry syrups were bioequivalent and had favorable safety profiles in Chinese healthy subjects in both fasted and fed states.

关 键 词：磷酸奥司他韦干糖浆 生物等效性 药代动力学 安全性 液相色谱-质谱法 

分 类 号：R978.7[医药卫生—药品]