复方磺胺甲噁唑片在中国健康受试者体内生物等效性研究  

Bioequivalence of compound sulfamethoxazole tablets in healthy Chinese subjects

作　　者：张天财 刘峻宇 张柏娥 赵沛月 王莹[3] 王慧琪 李亚飞 孙敏 ZHANG Tian-cai;LIU Jun-yu;ZHANG Bai-e;ZHAO Pei-yue;WANG Ying;WANG Hui-qi;LI Ya-fei;SUN Min(Yunnan Institute of Materia Medica,Kunming 650111,Yunnan Province,China;Yunnan Province Company Key Laboratory for TCM and Ethnic Drug of New Drug Creation,Kunming 650111,Yunnan Province,China;PhaseI Clinical Research Center,Zhejiang Provincial People's Hospital,Hangzhou 310014,Zhejiang Province,China)

机构地区：[1]云南省药物研究所,云南昆明650111 [2]云南省中药和民族药新药创制企业重点实验室,云南昆明650111 [3]浙江省人民医院Ⅰ期临床研究中心,浙江杭州310014

出　　处：《中国临床药理学杂志》2023年第20期2980-2984,共5页The Chinese Journal of Clinical Pharmacology

基　　金：科技人才与平台计划基金资助项目(202205AD160044)。

摘　　要：目的 评价2种复方磺胺甲噁唑片在中国健康人体内的生物等效性及安全性。方法 采用单中心、随机、开放、单剂量、双周期、双交叉设计。受试者空腹条件下单次口服受试制剂和参比制剂1片(磺胺甲噁唑0.40 g,甲氧苄啶80.00 mg),清洗期7 d,用液相色谱-串联质谱(LC-MS/MS)法测定人血浆中磺胺甲噁唑、甲氧苄啶的浓度,计算药代动力学参数。用WinNonlin8.1进行参数计算,进行生物等效性评价。结果 受试者服用受试制剂和参比制剂后,磺胺甲噁唑的主要药代动学参数:C_(max)分别为(27 035.48±3 827.14)和(29 681.25±4 514.52)ng·mL^(-1);AUC_(0-t)分别为(373 036.67±34 094.00)和(380 439.22±43 213.34)ng·h·mL^(-1);AUC_(0-∞)分别为(385 556.93±34 756.69)和(393 329.61±44 682.11)ng·h·mL^(-1);t_(max)分别为3.50和2.00 h。甲氧苄啶的主要药代动力学参数:C_(max)分别为(889.65±192.19)和(901.44±174.67)ng·mL^(-1);AUC_(0-t)分别为(9 222.04±1 965.38)和(8 993.56±1 899.98)ng·h·mL^(-1);AUC_(0-∞)分别为(9 357.82±2 028.06)和(9 118.71±1 959.42)ng·h·mL^(-1);t_(max)分别为1.00和0.88 h。磺胺甲噁唑C_(max)、AUC_(0-t)、AUC_(0-∞)的90%置信区间分别为88.49%~94.95%、96.40%~100.50%、96.28%~100.52%;甲氧苄啶C_(max)、AUC_(0-t)、AUC_(0-∞)的90%置信区间分别为92.97%~104.82%、99.70%~105.37%、99.76%~105.45%。结论 受试制剂和参比制剂的主要药代动力学参数相近,2种制剂具有生物等效性。Objective To evaluate the bioequivalence and safety of two kinds of compound sulfamethoxazole tablets in healthy Chinese subjects under fasting.Methods This study was designed as a single-center,randomized,open-label,single-dose,two-period,two-way crossover trail.A single oral dose of test formulation or reference formulation 1tablets[SMZ 0.40 g,trimethoprim (TMP) 80.00 mg]was given under fasting condition,and the cleaning period was 7 d.The drug concentration of SMZ and TMP in the plasma of healthy subjects was determined by LC-MS/MS,and the pharmacokinetic parameters were calculated by Win Nonlin8.1 software.Results After taking the test preparation and the reference preparation,the main pharmacokinetic parameters:C_(max)of SMZ were (27 035.48±3 827.14) and(29 681.25±4 514.52) ng·m L^(-1),respectively;AUC_(0-t)were(373 036.67±34 094) and (380 439.22±43 213.34) ng·h·m L^(-1),respectively;AUC_(0-∞)were (385 556.93±34 756.69) and (393 329.61±44 682.11) ng·h·m L^(-1),respectively;t_(max)were 3.50 and 2.00 h,respectively.The main pharmacokinetic parameters:C_(max)of TMP were (889.65±192.19)and (901.44±174.67) ng·m L^(-1),respectively;AUC_(0-t)were (9 222.04±1 965.38) and (8 993.56±1 899.98)ng·h·m L^(-1),respectively;AUC_(0-∞)were (9 357.82±2 028.06) and (9 118.71±1 959.42) ng·h·m L^(-1),respectively;t_(max)were 1.00 and 0.88 h,respectively.The main bioequivalence indicators were as follows:The 90%confidence interval C_(max),AUC_(0-t),AUC_(0-∞)of SMZ was 88.49%-94.95%,96.40%-100.50%,96.28%-100.52%,respectively.The 90%confidence interval C_(max),AUC_(0-t),AUC_(0-∞)of TMP was 92.97%-104.82%,99.70%-105.37%,99.76%-105.45%,respectively.Conclusion The main pharmacokinetic parameters of the test drug and the reference drug were similar,and the two preparations had bioequivalence.

关 键 词：磺胺甲噁唑 甲氧苄啶 生物等效 中国健康受试者 

分 类 号：R97[医药卫生—药品]