普卢利沙星片的药代动力学研究  

Pharmacokinetics of prulifloxacin tablets

作　　者：余建国[1] 孙华[2] 裘福荣[2,3] 

机构地区：[1]皖南医学院附属弋矶山医院药剂科,安徽芜湖241001 [2]皖南医学院附属弋矶山医院临床药学部,安徽芜湖241001 [3]上海中医药大学附属曙光医院临床药理科,上海201203

出　　处：《皖南医学院学报》2013年第3期191-194,共4页Journal of Wannan Medical College

摘　　要：目的:建立人血浆中普卢利沙星活性代谢产物NM394的HPLC测定法,并用于普卢利沙星片在中国健康志愿者体内药动学特征的研究。方法:健康志愿者10名(男女各半),单次和连续口服普卢利沙星片(200 mg/片),反相高效液相色谱法测定给药后血药浓度,DAS 2.1软件计算药代动力学参数。前处理采用高氯酸沉淀蛋白外标法,色谱柱为Lichrospher C18(150 mm×4.6 mm,5μm);流动相为0.025mol/L NaH2PO4(pH为2.75);流速1 ml/min;检测波长275nm。结果:NM394在0.03～3μg/ml范围内线性良好(r2=0.9987),血浆中低、中、高3种质量浓度的相对回收率在91.2%～113.2%之间;批内RSD≤6.8%、批间RSD≤8.5%。主要药动学参数为单次给药,女:t1/2(5.24±0.58)h、Cmax(1.64±0.76)μg/ml、AUC(0-18)(7.11±2.10)μg.h/ml;男:t1/2(5.22±0.74)h、Cmax(1.89±0.68)μg/ml、AUC(0-18)(7.80±0.93)μg.h/ml;两者无明显差异。多次给药达稳态后,女:t1/2(5.15±1.18)h、AUCss(9.26±1.35)μg.h/ml、DF(1.94±0.10);男:t1/2(5.10±0.27)h、AUCss(8.31±1.98)μg.h/ml、DF(2.04±0.60);两者无明显差异。单次给药与连续给药达稳态后药动学参数无明显差异。结论:本法简便、快速、稳定;无论单次给药还是连续给药,普卢利沙星的药动学特征无明显性别差异;多次用药后体内无明显蓄积现象;本品无明显肝药酶诱导或抑制作用。Objective：To develop a high performance liquid chromatogra- phy（HPLC） method for determination of the active metabolite （NM394） of prulifloxacin in human plasma and observe the pharmacokinetics of domestic prulifloxacin tablet in Chinese healthy volunteers. Methods ： A single oral dose and multi-dose of 200 mg prulifloxacin were administered in 10 healthy volunteers （male to female ratio：50% to 50% ）. Blood drug level was determined with HPLC, which entailed direct injection of the plasma sample after deproteination using perchloric acid by external reference. Chromatographic separation was achieved with a reversed-phase C18 column and a mobile phase of acetonitrile-phosphate buffer （ pH 2.75 ; 25 mmol/L） （20： 80,v/v）. Analysis was run at a flow-rate of 1.0 ml/min with ultraviolet detector set at wavelength of 275 nm. The pharmaeokinetic parameters were calculated with software DAS 2.1. Results ： The calibration curve was linear over the range of 0.03 - 3 μg/ml （ r2 = 0. 9987 ） , and the relative recoveries of low, medium and high concentration were within 91.2% - 113.2%. The intra-batch and inter-batch RSD were less than 6.7% and 8.5%, respectively. The main pharmacokinetic parameters of NM394 were ： t1/2 （5.24 ± 0.58 ） h, Cmax （ 1.64 ± 0.76 ） μg/ml, AUC（0-18） （7.11 ±2.10） μg · h/ml for females and tl/2 （5.22 ±0.74） h, Cmax, （ 1.89 ± 0.68 ）μg · h/ml, AUC 〈0 - 18） （7.80 ± 0.93 ）μg · h/ml for males in single dose;t1/2 （5.15 ± 1.18） h,AUC18 （9.26 ± 1.35） μg · h/ml,DF（1.94 ±0.10） for females and t1/2 （5.10 ±0.27） h,AUCss （ 8.31 ± 1.98 ） μg · h/ml, DF （ 2.04 ± 0.60 ） for males in multi-dose. No significant difference was found between males and females as well as single and multi-dosage. Conclusion：The assay method is simple, accurate and quick for investigation of the pharmacokinetics of prulifloxacin. Besides, there is neither cumulation of NM394 in the plasma after multiple dose of 200 mg nor liver

关 键 词：普卢利沙星 NM394 高效液相色谱法 药代动力学 

分 类 号：R969.1[医药卫生—药理学]