摘要
目的研究单剂量口服复方磺胺甲噁唑片在中国健康人体内的药动学特征,并评价两种制剂的生物等效性及安全性。方法采用单中心、随机、开放、两周期、自身交叉的试验设计,空腹条件下入组32名受试者,随机单次口服受试制剂和参比制剂1片(磺胺甲噁唑0.4 g,甲氧苄啶80 mg),采用LC-MS/MS法测定健康受试者血浆中磺胺甲噁唑和甲氧苄啶的药物浓度,采用WinNonlin软件进行药动学参数的计算,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动学参数C_(max)分别为(29.2±4.6)和(30.8±5.3)μg·mL^(-1);AUC_(0~t)分别为(430.5±66.8)和(430.2±59.4)h·μg·m L-1;AUC_(0~∞)分别为(450.9±73.7)和(449.6±65.7)h·μg·mL^(-1);t_(max)分别为3.0(1.5~5.0)h和2.5(0.7~5.0)h。甲氧苄啶的主要药动学参数C_(max)分别为(1.1±0.2)和(1.1±0.2)μg·mL^(-1);AUC_(0~t)分别为(10.7±2.7)和(10.5±2.5)h·μg·mL^(-1);AUC_(0~∞)分别为(11.1±2.7)和(10.9±2.4)h·μg·mL^(-1);t_(max)分别为1.0(0.5~3.5)h和0.7(0.5~3.5)h。结论两种复方磺胺甲噁唑片在中国健康受试者中具有生物等效性。
Objective To determine the pharmacokinetic characteristics of single dose oral administration compound sulfamethoxazole(SMZ)tablets in healthy Chinese people,and to evaluate the bioequivalence and safety of two preparations.Methods A single-center,randomized,open,two-cycle,self-crossover design was adopted.Totally 32 subjects were enrolled under fasting condition.One test preparation or one reference preparation[SMZ 0.4 g,trimethoprim(TMP)80mg]was taken orally at random.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 WinNonlin software.Results After taking the test preparation and the reference preparation,the main pharmacokinetic parameters Cmax of SMZ was(29.2±4.6)and(30.8±5.3)μg·m L-1,respectively.AUC0~t was(430.5±66.8)and(430.2±59.4)h·μg·mL^(-1),respectively.AUC0~∞was(450.9±73.7)and(449.6±65.7)h·μg·mL^(-1).tmax was 3.0(1.5~5.0)h and 2.5(0.7~5.0)h.The main pharmacokinetic parameters Cmax of TMP was(1.1±0.2)and(1.1±0.2)μg·mL^(-1).AUC0~t was(10.7±2.7)and(10.5±2.5)h·μg·mL^(-1).AUC0~∞was(11.1±2.7)and(10.9±2.4)h·μg·m L-1.tmax was 1.0(0.5~3.5)h and 0.7(0.5~3.5)h,respectively.Conclusion The two tablets are bioequivalent in Chinese healthy volunteers.
作者
吴蔚
肖珍
张顺芝
曹天然
黄庆
张小敏
鲁萍
WU Wei;XIAO Zhen;ZHANG Shun-zhi;CAO Tian-ran;HUANG Qing;ZHANG Xiao-min;LU Ping(The First Hospital of Changsha,Changsha 410013)
出处
《中南药学》
CAS
2021年第12期2555-2559,共5页
Central South Pharmacy
基金
湖南省卫生健康委科研计划项目资助项目(No.202113010356)
湖南省自然科学基金项目(No.2021JJ80017)。
