吡嗪酰胺片在中国健康受试者中的生物等效性研究  

Bioequivalence study of pyrazinamide tablets in Chinese healthy subjects

作　　者：叶丽冰 姚冲[2] 陈莹蓉[1] 童陆媛 杨涛 鲁潇 徐敏[1] 金秋月[1] 杨水新[1] YE Li-bing;YAO Chong;CHEN Ying-rong;TONG Lu-yuan;YANG Tao;LU Xiao;XU Min;JIN Qiu-yue;YANG Shui-xin(Clinical Trial Center,Department of Pharmacy,Huzhou Central Hospital,Huzhou 313000,Zhejiang Province,China;Department of Scientific Research,Huzhou Central Hospital,Huzhou 313000,Zhejiang Province,China;Department of Infectious Disease,Huzhou Central Hospital,Huzhou 313000,Zhejiang Province,China;Zhejiang SUKEAN Pharmaceutical Co.,Ltd.Hangzhou 310000,2Zhejiang Province,China)

机构地区：[1]湖州市中心医院药学部临床试验中心,浙江湖州313000 [2]湖州市中心医院科研部,浙江湖州313000 [3]湖州市中心医院感染科,浙江湖州313000 [4]浙江苏可安药业有限公司,浙江杭州310000

出　　处：《中国临床药理学杂志》2024年第15期2236-2240,共5页The Chinese Journal of Clinical Pharmacology

基　　金：湖州市科技计划公益性应用研究基金资助项目(2021GZ71)。

摘　　要：目的评价2种吡嗪酰胺片在中国健康受试者中的生物等效性及安全性。方法用开放、随机、单剂量、两序列、两周期、双交叉试验设计,48例受试者(空腹、餐后试验各24例)每周期单次口服吡嗪酰胺片受试制剂或参比制剂0.5 g。用液相色谱串联质谱法测定血浆中吡嗪酰胺的浓度,用WinNonlin v8.2软件计算药代动力学参数,用SAS 9.4软件进行生物等效性评价。结果在空腹试验中,吡嗪酰胺片受试制剂和参比制剂的C_(max)分别为(13.28±2.82)和(12.88±4.49)μg·mL^(-1),AUC_(0-t)分别为(139.17±26.58)和(138.63±28.92)h·μg·mL^(-1),AUC_(0-∞)分别为(148.96±33.65)和(148.71±36.97)h·μg·mL^(-1)。在餐后试验中,吡嗪酰胺片受试制剂和参比制剂的C_(max)分别为(11.89±1.96)和(11.99±1.92)μg·mL^(-1),AUC_(0-t)分别为(138.22±37.21)和(141.68±25.80)h·μg·mL^(-1),AUC_(0-∞)分别为(152.20±32.41)和(151.04±28.05)h·μg·mL^(-1)。在空腹和餐后条件下,C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值比的90%置信区间均落于80.00%~125.00%。空腹试验中,受试制剂和参比制剂不良事件发生率均为16.70%;在餐后试验中,受试制剂和参比制剂不良事件发生率均为8.30%。所有不良事件的严重程度均为轻度。结论吡嗪酰胺片受试制剂和参比制剂在健康受试者空腹和餐后状态下均具有生物等效性,且安全性良好。Objective To evaluate the bioequivalence and safety of two pyrazinamide tablets in healthy Chinese subjects.Methods An open,randomized,single-dose,two-sequence,two-cycle,double-cross trial design was used.All 48 healthy subjects(24 in fasting and 24 in fed trial)were randomized to receive a single oral dose of a 0.5 g pyrazinamide tablet(test or reference)per cycle.The plasma concentration of the drug was determined by liquid chromatography coupled to tandem mass spectrometry method.The pharmacokinetic parameters were calculated by WinNonlin v8.2,and the bioequivalence was evaluated by SAS 9.4.Results In the fasting group,the C_(max) of the test and reference preparation of pyrazinamide tablets were(13.28±2.82)and(12.88±4.49)μg·mL^(-1),the AUC0-t were(139.17±26.58)and(138.63±28.92)h·μg·mL^(-1),the AUC_(0-∞)were(148.96±33.65)and(148.71±36.97)h·μg·mL^(-1) respectively.In the fed group,the C_(max) of the test and reference preparation of pyrazinamide tablets were(11.89±1.96)and(11.99±1.92)μg·mL^(-1),the AUC0-t were(138.22±37.21)and(141.68±25.80)h·μg·mL^(-1),the AUC_(0-∞)were(152.20±32.41)and(151.04±28.05)h·μg·mL^(-1),respectively.The 90% confidence intervals of C_(max),AUC_(0-t) and AUC_(0-∞)geometric mean ratios of the test and reference preparation were all within 80.00% to 125.00%.The incidence of adverse events was 16.70% for both the test and reference preparation in the fasting group and 8.30% for both the test and reference preparation in the fed group,all of which were mild in severity.Conclusion The test and reference preparation of pyrazinamide tablets were bioequivalent,safe and well tolerated in healthy Chinese subjects under fasting and fed conditions.

关 键 词：吡嗪酰胺片 药代动力学 生物等效性 液相色谱串联质谱法 

分 类 号：R978.3[医药卫生—药品]