血浆普卢利沙星活性代谢物的测定及其人体药动学研究  

Evaluation for the active metabolites and pharmacokinetics of prulifloxacin in Chinese healthy volunteers

作　　者：江丽[1] 杭太俊[1] 沈建平[2] 张银娣[2] 

机构地区：[1]中国药科大学药物分析教研室,南京210009 [2]南京医科大学临床药理研究所,南京210029

出　　处：《中国新药杂志》2006年第4期307-310,共4页Chinese Journal of New Drugs

摘　　要：目的:建立人血浆普卢利沙星活性代谢物(UFX)浓度的高效液相色谱测定法,研究普卢利沙星片在健康人体内的药动学。方法:10例健康志愿受试者分别服用普卢利沙星片(相当于UFX为200 mg)单剂量和连续多次给药达稳态时进行药动学研究。血浆样品经甲醇沉淀蛋白,以Zorbax ODS柱、甲醇-0．015 mol·L^(-1)磷酸二氢钾缓冲溶液(pH 3．0)为流动相(35:65),进行HPLC荧光检测分析,测定血浆普卢利沙星活性代谢物浓度经时过程,并计算药动学参数。结果:HPLC测定血浆UFX的色谱峰面积与浓度在0．025～3．00μg·mL^(-1)范围线性关系良好,最低定量限浓度为0．025μg·mL^(-1)。血浆样品分析的回收率、精密度和准确度均良好。受试者单剂量口服普卢利沙星片后与UFX相应的主要药动学参数为C_(max)(1．48±0．44)μg·mL^(-1),T_(max)(0．9±0．8)h,AUC_(0-36h)(6．74±0．96) h·μg·mL^(-1),AUC_(0-∞)(6．97±1．06)h·μg·mL^(-1),t_(1/2)(7．21±1．60)h,MRT(8．44±1．94)h;口服普卢利沙星片达稳态后,C_(max)(1．34±0．41)μg·mL^(-1),T_(max)(0．9±0．4)h,AUC_(0-36h)(8．46±1．43)h·μg·mL^(-1),AUC_(0-∞)(8．61±1．43)h·μg·mL^(-1),t_(1/2)(6．27±0．86)h,MRT(8．38±0．94)h。结论:建立的HPLC荧光测定法专属准确,灵敏度适宜,测得的药动学参数可为普卢利沙星临床用药提供了参考依据。Objective：To determine the active metabolites （UFX） and pharmacokinetics of prulifloxaein in healthy Chinese volunteers. Method： Ten healthy volunteers were randomly administered with either a single dose or multiple doses of prulifloxaein tablets （ equivalent to UFX 200 mg each time） to investigate the pharmaeokinetic profiles. The blood samples from the volunteers were treated with methanol to precipitate proteins. Subsequently, the plasma concentrations of UFX were determined by HPLC consisted of an Agilent Zorbax C 18 column, an eluate of methanol-0. 015 mol·L^-1 phosphate buffer （pH 3. 0, 35： 65） and fluoreseence detection. The blood samples from the volunteers with multiple doses were collected and quantified until the drug concentrations accumulated and increased to a steady-state level. Resuits： A calibrated linear curve of UFX was in the range of 0. 025 - 3. 00μg· mL^- 1. The detection limit was 0. 025μg· mL^-1. The main pharmacokinetic parameters of UFX for the single dose and muhiple doses （steady state） were as follows： Cmax（1.48 ±0.44） vs. （1.34 ±0.41）μg·mL^-1, Tmax（0.9 ±0.8） vs. （0.9±0.4） h, AUC0- 36h（6.74±0.96） vs. （8. 46±1.43） h·μg·mL^-1, AUC0-∞（6.97±1.06） vs. （8161 ±1.43）h·μg·mL^-1, t1/z（7.21 ±1.60） vs. （6.27±0.86） h and MRT （8.44±1.94） vs. （8.38 ±0.94） h. Conclusion： The pharmaeokinetic parameters determined by the sensitive and specific HPLC-fluoreseence detection could serve as a monitoring tool for the pharmacotherapeuties of prulifloxacin.

关 键 词：普卢利沙星 活性代谢物UFX 药动学 高效液相色谱 

分 类 号：R969.1[医药卫生—药理学] R978.27[医药卫生—药学]