磷酸特地唑胺片在中国健康受试者中的生物等效性研究  

Bioequivalence study of tedizolid phosphate tablets in Chinese healthy subjects

作　　者：裴莹子 陈松[2] 赵晓 高丽静 杨少杰[2] 王庆[2] 杨甫德[2] 田宝朋 谭云龙[2] PEI Ying-zi;CHEN Song;ZHAO Xiao;GAO Li-jing;YANG Shao-jie;WANG Qing;YANG Fu-de;TIAN Bao-peng;TAN Yun-long(Beijing Fuyuan Pharmaceutical Company Limited,Beijing 101113,China;PhaseⅠClinical Trial Center,Beijing Huilongguan Hospital,Beijing 100096,China)

机构地区：[1]北京福元医药股份有限公司,北京101113 [2]北京回龙观医院药物Ⅰ期临床试验研究室,北京100096

出　　处：《中国临床药理学杂志》2023年第5期733-737,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评估2种磷酸特地唑胺片200 mg在中国健康受试者中的生物等效性及安全性。方法本研究采用开放、随机、双周期、双交叉设计,空腹组和餐后组均纳入24例健康成年受试者分别单次口服磷酸特地唑胺片受试制剂或参比制剂200 mg。用LC-MS/MS法测定血浆中特地唑胺的浓度,用SAS 9.4处理血浆中特地唑胺的浓度-时间数据,以非房室模型法计算特地唑胺药代动力学参数,并进行生物等效性及安全性评价。结果空腹试验受试制剂和参比制剂的特地唑胺C_(max)分别为(2405.00±433.00)和(2409.00±469.00)ng·mL^(-1),t_(max)分别为3.00和1.50 h,t_(1/2)分别为(9.84±1.30)和(9.86±1.05)h,AUC_(0-t)分别为(26578.00±7127.00)和(26322.00±6358.00)ng·mL^(-1)·h,AUC_(0-∞)分别为(27612.00±7706.00)和(27301.00±6800.00)ng·mL^(-1)·h;餐后试验受试制剂和参比制剂的特地唑胺C_(max)分别为(2218.00±426.00)和(2201.00±343.00)ng·mL^(-1),t_(max)分别为3.25和3.00 h,t_(1/2)分别为(9.92±1.19)和(10.03±1.29)h,AUC_(0-t)分别为(28635.00±5407.00)和(28605.00±5677.00)ng·mL^(-1)·h,AUC_(0-∞)分别为(29784.00±5878.00)和(29790.00±6200.00)ng·mL^(-1)·h。空腹组和餐后组受试制剂和参比制剂主要药代动力学参数的几何均值比值的90%置信区间均落在80.00%~125.00%。空腹组和餐后组不良事件发生率分别为20.83%和45.83%。结论中国受试者在空腹与餐后状态下,单次口服受试和参比磷酸特地唑胺片均具生物等效性,且安全性良好。Objective To evaluate the bioequivalence and safety of two tedizolid phosphate tablets 200 mg in healthy Chinese subjects.Methods This study was an open-lable,randomized,two-period crossover design.A total of 24 subjects respectively for fasting and fed state were given a single oral dose of test or reference tedizolid phosphate tablets 200mg.The plasma concentration of tedizolid was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS),and the concentration-time data was processed by SAS 9.4,the model method of the non-compartmental was used to calculate the pharmacokinetic parameters of tedizolid and to evaluate the bioequivalence.Results Under fasting state,the C_(max)of tedizolid test and reference were(2405.00±433.00)and(2409.00±469.00)ng·mL^(-1),t_(max)were3.00 and 1.50 h,t_(1/2)were(9.84±1.30)and(9.86±1.05)h,AUC_(0-t)were(26578.00±7127.00)and(26322.00±6358.00)ng·mL^(-1)·h,AUC_(0-∞)were(27612.00±7706.00)and(27301.00±6800.00)ng·mL^(-1)·h.The main pharmacokinetic parameters of tedizolid test and reference under fed state were C_(max)(2218.00±426.00)and(2201.00±343.00)ng·mL^(-1),t_(max)3.25 and 3.00 h,t_(1/2)(9.92±1.19)and(10.03±1.29)h,AUC_(0-t)(28635.00±5407.00)and(28605.00±5677.00)ng·mL^(-1)·h,AUC_(0-∞)(29784.00±5878.00)and(29790.00±6200.00)ng·mL^(-1)·h.Under fasting and fed conditions,the90%confidence intervals of the geometric mean ratios of the main pharmacokinetic parameters of the test drug and reference drug were within the range of 80.00%to 125.00%.The incidences of adverse events in the fasting group and the fed group were 20.83%and 45.83%,respectively.Conclusion Single oral test and reference tedizolid phosphate tablets were bioequivalent and safe under both fasting and fed conditions in healthy Chinese subjects.

关 键 词：磷酸特地唑胺片 健康受试者 生物等效性 药代动力学 LC-MS/MS 

分 类 号：R969[医药卫生—药理学]