高效液相色谱荧光法测定血浆中左氧氟沙星的浓度及其生物等效性研究

Determination of levofloxacin concentration in plasma of Chinese healthy volunteers by HPLC with fluorescence detection and bioequivalence study of levofloxacin hydrochloride tablets

目的：建立高效液相色谱（HPLC）荧光法测定血浆中左氧氟沙星的浓度，研究盐酸左氧氟沙星片在健康人体中的生物等效性。方法采用随机交叉自身对照试验设计，24名健康男性受试者单次口服0．2 g盐酸左氧氟沙星片受试制剂或参比制剂，分别于不同时间点采集肘静脉血，采用HPLC荧光法测定血浆中左氧氟沙星的药物浓度。利用DAS 2．0软件计算药动学参数，评价两制剂的生物等效性。结果受试制剂与参比制剂的主要药动学参数 t1／2、tmax 、ρmax 、AUC0唱36和 AUC0唱inf分别为（6．71±0．95）h和（6．60±1．00）h；（0．85±0．30）h 和（0．79±0．28）h ；（2815．48±513．04）ng／ml和（3185．59±674.29） ng／ml；（17157．61±1949．07） ng · h／ml和（17425．06±2447．80） ng · h／ml；（18324．52±2019．41） ng · h／ml和（18540．41±2523．08） ng · h／ml。两制剂主要药动学参数统计学分析无显著性差异。受试制剂与参比制剂 AUC0-36、AUC0-inf和ρmax对数比值的90％置信区间分别为95．2％-102．5％、96．1％-102．2％和82．8％-94.9％。结论受试制剂与参比制剂具有生物等效性，为生物等效制剂。

Objective To develop a HPLC-fluorescence method to determine levofloxacin concentration in plasma for studying bioequivalence of levofloxacin hydrochloride tablet in Chinese healthy volunteers .Methods A single-dose of 0 .2 g test or reference preparation was given to 24 healthy volunteers in a randomized crossover study .The concentrations of levofloxacin at different time points were determined by HPLC with fluorescence detection .The pharmacokinetic parameters were calculated using DAS 2 .0 software program .Results The main pharmacokinetic parameters of the test and reference preparation ,t 1/2 、tmax 、ρmax 、AUC0-36 and AUC0-inf ,were respectively （6 .71 ± 0 .95） h and （6 .60 ± 1 .00） h ,（0 .85 ± 0 .30） h and （0 .79 ± 0 .28） h , （2 815 .48 ± 513 .04 ） ng/ml and （3 185 .59 ± 674 .29 ） ng/ml ,（17 157 .61 ± 1 949 .07 ） ng · h/ml and （17 425 .06 ± 2 447 .80） ng · h/ml ,（18 324 .52 ± 2 019 .41） ng · h/ml and （18 540 .41 ± 2 523 .08） ng · h/ml .The statistical analysis showed that the main pharmacokinetic parameters between test and reference preparations were no significant differences .The 90% confidence interval of test and reference preparations AUC 0-36 、AUC0-inf and ρmax were 95 .2% -102 .5% 、96 .1% -102 .2%and 82 .8% -94.9% .Conclusion The test and reference preparations were bioequivalent .