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。
Abstract
Objective To study the bioequivalence of moxifloxacin tablets (test tablets) compared with the innovator preparation (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 pharmacokinetic 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 preparation, 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.
关键词
莫西沙星 /
生物等效性 /
健康人体
Key words
moxifloxacin /
bioequivalence /
healthy body
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