盐酸莫西沙星片健康人体生物等效性研究

摘要

Objective To study the bioequivalence of moxifloxacin tablets ( test tablets) compared with the innovator prepara-tion ( reference tablets) in Chinese healthy volunteers.Methods Randomized, positive control, open, three-cross clinical trials were performed.24 healthy subjects were randomized to undergo three crossover oral test drugs including moxifloxacin 400 mg ( TA ) , 200 mg*2(TB) and the reference drug 400 mg (RC).A 4 ml blood sample was taken at every time at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 32 and 48 h before and after treatment.The plasma concentration of moxifloxacin was determined by RP-HPLC, fluorescence detection and internal standard-standard curve method.DAS 2.1.1 software was used to calculate the pharmaco-kinetic parameters and evaluate the bioequivalence.Results Pharmacokinetic parameters for the TA were Cmax (4.150 ±1.17) μg/ml,Tmax(1.646 ±0.94) h,AUC0-t(47.163 ±6.14) μg· h/ml,AUC0-∞(50.171 ±7.01)μg· h/ml.Pharmacokinetic parameters for the TB were Cmax(3.719 ±0.94) μg/ml,Tmax(1.656 ±0.99) h,AUC0-t(46.686 ±6.01) μg· h/ml,AUC0-∞(49.737 ±7.15)μg· h/ml.Pharmacokinetic parameters for the RC were Cmax (3.827 ±0.78)μg/ml,Tmax (1.625 ±1.01) h,AUC0-t (46.281 ±6.02) μg· h/ml,AUC0-∞(49.276 ±6.97)μg· h/ml.The three groups had no statistical difference by the analysis of variance, and the two-way unilateral t-test results showed that the test preparation did not exceed the prescribed upper limit and lower limit of the reference prepa-ration, rejecting null hypothesis (P<0.05).The 90%confidence interval of Cmax,Tmax,AUC0-t and AUC0-∞were between the standard of reference tablets ( 80%-125%) .Conclusions The pharmacokinetic parameters of TA , TB are conform to the biological equivalent decision criteria compared with RC.%目的：探索国产莫西沙星片与原研产品“拜复乐”是否具有生物等效性。方法采取随机、阳性对照、开放、自身三交叉的临床试验研究，24名健康受试者随机三交叉口服试验药物莫西沙星400 mg（ TA ）、200 mg ×2片（ TB ）及参照药品“拜复乐”400 mg（RC），清洗期1周，受试者于3次用药前和用药后0．25、0．5、0．75、1、1．5、2、2．5、3、4、6、8、12、24、32和48 h于上肢静脉取血4 ml，应用RP-HPLC、荧光检测、内标-标准曲线法测定血药浓度，采用DAS 2．1．1程序拟合药动学参数，并进行生物等效性评价。结果 TA 的药动学参数为Cmax（4．15±1．17）μg／ml，Tmax（1．64±0．94） h，AUC0-t（47．16±6．14）μg· h／ml，AUC0-∞（50．17±7．01）μg· h／ml；TB 的药动学参数为，Cmax（3．71±0．94）μg／ml，Tmax（1．65±0．99）h，AUC0-t（46．68±6．01）μg· h／ml，AUC0-∞（49．73±7．15）μg· h／ml；RC的药动学参数为，Cmax（3．82±0．78）μg／ml，Tmax（1．62±1．01） h，AUC0-t（46．28±6．02）μg· h／ml，AUC0-∞（49．27±6．97）μg· h／ml，经方差分析，三组无统计学差异，经双向单侧t检验结果表明，受试制剂没有超过规定的参比制剂的高限和低限，差异无统计学意义；90％置信区间计算结果表明受试制剂Cmax、Tmax、AUC0-t和AUC0-∞均数为参比制剂均数的80％～125％。结论 TA、TB 的药动学参数AUC0-t、AUC0-∞、Cmax和Tmax与RC比较均符合生物等效的判定标准。