对乙酰氨基酚干混悬剂在健康人体内的药动学和生物等效性研究  

Pharmacokinetics and bioequivalence of paracetamol suspension in Chinese healthy volunteers

作　　者：郭伟一 冯仕银 蔡林芮[1,2,3] 邹琴 陈卓[1,2,3] 苏旭 杜丹[1,2,3] 余勤 GUO Wei-yi;FENG Shi-yin;CAI Lin-rui;ZOU Qin;CHEN Zhuo;SU Xu;DU Dan;YU Qin(Institute of Drug Clinical Trial.GCP,West China Second University Hospital,Sichuan University,Chengdu 610041,China;Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation,West China Second University Hospital,Chengdu 610041,China;Key Laboratory of Birth Defects and Related Disease of Women and Children,Ministry of Education,West China Second University Hospital,Chengdu 610041,China)

机构地区：[1]四川大学华西第二医院国家药物临床试验机构,成都610041 [2]四川大学华西第二医院药物制剂体内外相关性技术研究重点实验室,成都610041 [3]四川大学华西第二医院出生缺陷与相关妇儿疾病教育部重点实验室,成都610041

出　　处：《中国新药杂志》2024年第7期682-687,共6页Chinese Journal of New Drugs

摘　　要：目的:评价健康受试者空腹和餐后条件下单次口服对乙酰氨基酚干混悬剂受试制剂和参比制剂的生物等效性。方法:空腹/餐后各26例健康受试者口服受试制剂对乙酰氨基酚干混悬剂和参比制剂对乙酰氨基酚细粒剂(CALONAL^(?) Fine Gran),采用单次口服、单中心、随机、开放、双周期、交叉设计,用HPLC-MS/MS法检测血浆中对乙酰氨基酚浓度,使用Phoenix WinNonlin 8.1软件及SAS 9.4软件分析生物等效性(BE)。结果:空腹组26例健康受试者分别单次空腹服用对乙酰氨基酚干混悬剂(受试制剂)和对乙酰氨基酚细粒剂(参比制剂)后,C_(max),AUC_(0~t)及AUC_(0~∞)的几何均数比值及其90%置信区间分别为100.72%(90.88%,111.63%),96.55%(92.80%,100.46%),95.58%(92.78%,98.48%),均落在等效区间80.0%~125.00%范围内。餐后组26例健康受试者在餐后口服对乙酰氨基酚干混悬剂(受试制剂)和对乙酰氨基酚细粒剂(参比制剂)后,C_(max),AUC_(0~t)及AUC_(0~∞)的几何均数比值及其90%置信区间分别为96.69%(89.52%,104.43%),98.27%(95.63%,100.98%),98.59%(96.01%,101.24%),均落在等效区间80.0%~125.00%范围内。结论:2种制剂在空腹和餐后条件下具有生物等效性。Objective:To evaluate the bioequivalence between a single test and reference dose of Paracetamol Suspension in healthy volunteers under the fasting and fed conditions.Methods:A randomized,open label,single-dose,self-crossover design was performed.HPLC-MS/MS was applied to detect the concentrations of acetamidophenol in the plasma of healthy subjects under the fasting and fed conditions.Phoenix WinNonlin 8.1 and SAS 9.4 software were used for PK parameters calculation and bioequivalence analysis.Results:Under the fasting condition,13 healthy subjects were administered by test and 13 by reference preparation.The ratio of the geometric mean and 90% confidence interval of C_(max),AUC_(0~t) and AUC_(0~∞) are 100.72%(90.88%,111.63%),96.55%(92.80%,100.46%),95.58%(92.78%,98.48%),respectively.All the data fell within the equivalent range of 80.0%~125.00%.Under the fed condition,13 healthy subjects were administered by test and 13 by reference preparation.The ratio of the geometric mean and 90% confidence interval of C_(max),AUC_(0~t) and AUC_(0~∞) are 96.69%(89.52%,104.43%),98.27%(95.63%,100.98%),98.59%(96.01%,101.24%).All the data fell within the equivalent range of 80.0%~125.00%.Conclusion:The two preparations are bioequivalent under fasting and fed conditions.

关 键 词：对乙酰氨基酚干混悬剂 空腹 餐后 生物等效性 药动学 

分 类 号：R969.4[医药卫生—药理学]