加替沙星在家兔体内的代谢动力学研究

Study on the Pharmacodynamics of Gatifloxacin in Rabbits

[目的]分析加替沙星在家兔体内的药代动力学过程。[方法]家兔口服5、10和20mg／kg加替沙星后于0．25、0．50、1．00、2．00、4．00、8．00、12．00和24．00h分别取静脉血，应用毛细管区带电泳-二极管阵列检测法测定血药浓度并计算代谢动力学参数。家兔口服10mg／kg加替沙星后于0．25、0．50、1．00、2．00和4．00h分别测定心、肺、肌肉等组织中的药物浓度。[结果]加替沙星在0．05～5．00μg／ml范围内具有良好线性关系，最低检测限为0．05μg/ml，在家兔血液代谢动力学过程符合一室模型。5、10和20mg/kg剂量组主要动力学参数如下：峰浓度（cmax）分别为2．28、3．35和7．93μg／ml；达峰时间（Tmax）分别为1．36、1．83和1．69h；吸收半衰期（t1/2Ka）分别为0．39、0．51和0．42h；消除半衰期（t1/2 Ke）分别为5．63、6．07和6．81h；药时曲线下面积（AUC）分别为21．67、33．59和97．07（μg·h）／ml。加替沙星被家兔摄入后，迅速分布于各组织中。[结论]加替沙星在家兔体内吸收迅速，消除半衰期长，组织分布广泛，是一种值得推广的新型氟喹诺酮类抗生素。

[ Objective ] The study aimed to analyze the pharmaeodynamics process of gatifloxacin in rabbits. [ Method ] Following the oral ad- ministration of a single dose of 5,10 and 20 mg/kg gatifloxacin to rabbits, their vein blood was selected resp. at 0. 25 ,0. 50,1. 00,2.00,4.00, 8.00,12.00 and 24.00 h after administration, and the gatifloxacin concn, in the plasma were determined by coupling capillary Zone Electrophoresis with Diode Array Detection （CZE-DAD） , resp. and then the pharmacodynamies parameters were calculated. After the oral administration of a single dose of 10 mg/kg gatifloxacin to the rabbits,the gatifloxaein eoncn, in different tissues such as heart,lung,muscle were de- termined resp. at O. 25,0.50,1.00,2.00,4. O0 h after administration. [ Result] The gatifloxacin had good linear relation over the range from 0.05 to 5.00μg/ml,with a detection limit of 0.05 μg/ml. The pharmacodynamics process of rabbits fitted to one compartment model. The main kinetic parameters for the dose groups at 5,10, and 20 mg/kg were follows ： Cmox were 2.28,3.35 and 7.93μg/ml resp. ; Tmax were 1.36, 1.83 and 1.69 h respe. ; t1/2Ka were 0.39,0.51 and 0.42 h resp. ; t1/2Ke were 5.63,6.07 and 6.81 h resp. ; AUC were 21.67,33.59 and 97.07 （μg·h）/ml resp. The gatifloxaein fed to rabbits was rapidly and extensively distributed to all tissues. [ Conclusion] The gatifloxaein was rapidly absorbed in rabbits ,with a longer t~/2Ke and extensive distribution ,which is a new and effective fluoro-guinolone antibiotic that was worth to be extended.