磷酸奥司他韦干混悬剂的人体药动学与生物等效性  

Pharmacokinetics and bioequivalence study of oseltamivir phosphate dry suspension in healthy Chinese subjects

作　　者：冯婉妮 金娟 朱昌海 王欣桐 周玲 彭杰敏 甘方良 FENG Wan-ni;JIN Juan;ZHU Chang-hai;WANG Xin-tong;ZHOU Ling;PENG Jie-min;GAN Fang-liang(Clinical Pharmacology Research Center,First Affiliated Hospital of Hubei University of Science and Technology,Hubei Xianning 437100,China;Hunan Provincial Key Laboratory for Bioanalysis of Complex Matrix Samples,Hunan Changsha 410000,China)

机构地区：[1]湖北科技学院附属第一医院临床药理研究中心,湖北咸宁437100 [2]复杂基质样本生物分析湖南省重点实验室,湖南长沙410000

出　　处：《中国医院药学杂志》2023年第5期519-524,共6页Chinese Journal of Hospital Pharmacy

摘　　要：目的:研究磷酸奥司他韦干混悬剂在健康受试者的人体药动学和生物等效性。方法:78例受试者分别空腹和餐后口服75 mg受试制剂或参比制剂。采用高效液相色谱-串联质谱(HPLC-MS/MS)检测奥司他韦和奥司他韦酸的全血浓度,用WinNonlin 8.2软件计算药动学参数,评价两制剂生物等效性。结果:空腹试验受试制剂和参比制剂的奥司他韦C_(max)、AUC_(0-t)、AUC_(0-∞)分别为(52.07±23.44)和(50.54±16.09)ng·mL^(-1)、(150.8±32.0)和(153.6±29.3)h·ng·mL^(-1)、(154.2±32.2)和(157.8±30.9)h·ng·mL^(-1);奥司他韦羧酸盐C_(max)、AUC_(0-t)、AUC_(0-∞)分别为(259.66±42.65)和(267.10±44.06)ng·mL^(-1)、(3235.1±549.9)和(3321.6±567.5)h·ng·mL^(-1)、(3284.2±564.9)和(3372.4±593.5)h·ng·mL^(-1);餐后试验受试制剂和参比制剂的奥司他韦C_(max)、AUC_(0-t)、AUC_(0-∞)分别为(40.56±10.72)和(38.82±10.98)ng·mL^(-1)、(145.4±24.5)和(145.3±28.7)h·ng·mL^(-1)、(151.2±25.4)和(149.0±28.5)h·ng·mL^(-1);奥司他韦羧酸盐C_(max)、AUC_(0-t)、AUC_(0-∞)分别为(198.12±34.65)和(199.56±36.39)ng·mL^(-1)、(2794.8±373.2)和(2828.1±416.5)h·ng·mL^(-1)、(2853.0±383.4)和(2885.9±423.2)h·ng·mL^(-1)。结论:受试制剂与参比制剂主要药动学参数的几何均值比值90%CI在80%~125%范围内,两制剂生物等效。OBJECTIVE To study the pharmacokinetics and bioequivalence of test preparation and reference preparation of oseltamivir phosphate dry suspension in healthy volunteers under fasted and fed conditions.METHODS Totally 78 subjects were orally administered 75 mg of the test preparation or the reference preparation under fasted and fed,respectively.High performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was used to detect the whole blood concentration of oseltamivir and oseltamivir acid,and WinNonlin 8.2 software was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the two preparations.RESULTS The major pharmacokinetic parameters of the test and reference oseltamivir under the fasted condition were as follows:C_(max)(52.07±23.44)and(50.54±16.09)ng·mL^(-1),AUC_(0-t)(150.8±32.0)and(153.6±29.3)h·ng·mL^(-1),AUC_(0-∞)(154.2±32.2)and(157.8±30.9)h·ng·mL^(-1).The major pharmacokinetic parameters of the test and reference oseltamivir carboxylate under the fasted condition were as follows:C_(max)(259.66±42.65)and(267.10±44.06)ng·mL^(-1),AUC_(0-t)(3235.1±549.9)and(3321.6±567.5)h·ng·mL^(-1),AUC_(0-∞)(3284.2±564.9)and(3372.4±593.5)h·ng·mL^(-1).The major pharmacokinetic parameters of the test and reference oseltamivir in the fed condition were as follows:C_(max)(40.56±10.72)and(38.82±10.98)ng·mL^(-1),AUC_(0-t)(145.4±24.5)and(145.3±28.7)h·ng·mL^(-1),AUC_(0-∞)(151.2±25.4)and(149.0±28.5)h·ng·mL^(-1).The major pharmacokinetic parameters of the test and reference oseltamivir carboxylate in the fed condition were as follows:C_(max)(198.12±34.65)and(199.56±36.39)ng·mL^(-1),AUC_(0-t)(2794.8±373.2)and(2828.1±416.5)h·ng·mL^(-1),AUC_(0-∞)(2853.0±383.4)and(2885.9±423.2)h·ng·mL^(-1).CONCLUSION The 90%CI of the geometric mean ratios of the test preparation and the reference preparation for the C_(max),AUC_(0-t)and AUC_(0-∞)of oseltamivir and oseltamivir acid under the fasted and fed conditions is within the range of 80%-125%,suggesting the

关 键 词：奥司他韦 生物等效性 药动学 干混悬剂 

分 类 号：R978.7[医药卫生—药品]