硫酸沙丁胺醇吸入气雾剂药动学等效性评价技术与流程研究  

Evaluation technology and process of pharmacokinetic bioequivalence of Salbutamol Sulfate Inhalation Aerosol

作　　者：刘义伟 何正 陈婧 陈倩[1] 任秀华[1] 丁玉峰 LIU Yi-wei;HE Zheng;CHEN Jing;CHEN Qian;REN Xiu-hua;DING Yu-feng(Department of Pharmacy,Affiliated Tongji Hospital,Tongji Medical College,Huazhong University of Science&Technology,Hubei Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院药学部,湖北武汉430030

出　　处：《中国医院药学杂志》2021年第8期777-782,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家科技重大专项课题:药物一致性评价关键技术与标准研究(编号:2017ZX09101001)。

摘　　要：目的:建立硫酸沙丁胺醇吸入气雾剂药动学等效性评价技术与流程。方法:6名健康受试者双周期空腹经口吸入硫酸沙丁胺醇吸入气雾剂200μg(2掀),2周期间清洗期为7 d。采用超高效液相色谱-质谱联用法测定人血浆中沙丁胺醇浓度。DAS 3.2.8软件统计血药浓度-时间数据。计算药动学参数C_(max)、AUC_(0-20 min)、AUC_(0-t)和AUC_(0-∞)及其个体内变异系数。结果:硫酸沙丁胺醇吸入气雾剂第一周期和第二周期的主要药动学参数C_(max)分别为(285.33±158.83)pg·mL^(-1)和(222.12±108.02)pg·mL^(-1),t_(max)分别为(0.72±0.52)h和(1.03±1.03)h,t_(1/2z)分别为(6.39±1.75)h和(5.91±1.22)h,AUC_(0-20 min)分别为(63.77±42.27)pg·h·mL^(-1)和(47.56±33.54)pg·h·mL^(-1),AUC_(0-t)分别为(1469.79±701.96)pg·h·mL^(-1)和(1292.24±498.59)pg·h·mL^(-1),AUC_(0-∞)分别为(1596.30±772.95)pg·h·mL^(-1)和(1383.21±488.82)pg·h·mL^(-1)。药动学参数C_(max)、AUC_(0-20 min)、AUC_(0-t)和AUC_(0-∞)的个体内变异系数分别为29.04%、17.64%、27.12%和27.63%。结论:本研究建立了一种简便、经济和准确的硫酸沙丁胺醇吸入气雾剂药动学等效性评价技术与流程。OBJECTIVE To establish the evaluation technology and process of pharmacokinetic bioequivalence for salbutamol Sulfate Inhalation Aerosol.METHODS Six healthy subjects orally inhaled 200μg(2 puffs)of Salbutamol Sulfate Inhalation Aerosol under fast condition in two study periods and the washout period between two study periods was 7 days.The concentration of salbutamol in human plasma was determined by ultra performance liquid chromatography-mass spectrometry.The plasma drug concentration-time data were statistically analyzed by the DAS 3.2.8 software.The pharmacokinetic parameters C_(max),AUC_(0-20 min),AUC_(0-t) and AUC_(0-∞)and their within-subject coefficient of variations were calculated.RESULTS The main pharmacokinetic parameters of Salbutamol Sulfate Inhalation Aerosol in the first period and the second period were C_(max),(285.33±158.83)vs(222.12±108.02)pg·mL^(-1);t_(max),(0.72±0.52)vs(1.03±1.03)h;t1/2 z,(6.39±1.75)vs(5.91±1.22)h;AUC_(0-20 min),(63.77±42.27)vs(47.56±33.54)pg·h·mL^(-1);AUC_(0-t),(1469.79±701.96)vs(1292.24±498.59)pg·h·mL^(-1);AUC_(0-∞),(1596.30±772.95)vs(1383.21±488.82)pg·h·mL^(-1).The within-subject coefficient of variations of pharmacokinetic parameters C_(max),AUC_(0-20 min),AUC_(0-t) and AUC_(0-∞)were 29.04%,17.64%,27.12%and 27.63%respectively.CONCLUSION This study has established a simple,economical and accurate technology and process for evaluating the pharmacokinetic equivalence of Salbutamol Sulfate Inhalation Aerosol.

关 键 词：硫酸沙丁胺醇吸入气雾剂 药动学等效性 评价技术与流程 个体内变异系数 

分 类 号：R945[医药卫生—微生物与生化药学]