异育银鲫体内盐酸双氟沙星血浆蛋白结合率的变化与其药代动力学研究

为了研究盐酸双氟沙星(difloxacin, DIF)在异育银鲫体内血浆蛋白结合率的变化及其与药代动力学之间的关系, 实验采用超滤法测定了DIF在异育银鲫体内血浆蛋白结合率, 运用HPLC测定其对应时间点药物浓度, 并分析了血浆蛋白结合率变化对DIF体内处置的影响。实验以感染嗜水气单胞菌的异育银鲫为感染组, 健康异育银鲫为对照组。结果显示: 感染组各时间点DIF血浆蛋白结合率均高于对照组, 感染组与对照组DIF血浆蛋白结合率与总药物浓度呈对数关系: y=-9.01ln x+74.34和y=-4.81ln x+65.15, DIF血浆蛋白结合率与游离药物浓度的对数关系式分别为: y=-6.36ln x+64.91和y=-4.36ln x+ 60.63; 感染组和对照组血浆药时曲线均可使用开放性二室模型描述; 感染组DIF的吸收和消除慢于对照组, 其表观分布容积和曲线下面积大于对照组。结果显示异育银鲫体内感染嗜水气单胞菌促使DIF血浆蛋白结合率升高; 血浆蛋白结合率升高导致药物以结合药物的形式储存于血液中可能是导致药物组织分布受限、消除缓慢、长时间滞留于血液原因之一。

RESEARCHES OF PLASMA PROTEIN BINDING RATE OF DIFLOXACIN AND ITS PHARMACOKINETIC IN CARASSAIS AURATUS GIBEBIO

To investigate the relationship between the diversities of plasma protein binding rate of Difloxacin (DIF) and its pharmacokinetic in Carassais auratus gibebio, ultrafilteration and high performance liquid chromatographic (HPLC) methods were applied to determine the plasma protein binding rate and pharmacokinetics of DIF in both infected by Aerominas hydrophila bacteria (infected group) and healthy Carassais auratus gibebio (healthy group), and the relationships between the diversities of plasma protein binding rate of DIF and its pharmacokinetic were analyzed in this paper. The results showed that the plasma protein binding rates of the drug in infected group was significantly higher than that of the healthy group at the corresponding time points. The plasma protein binding rates had logarithmic relationships with the total drug concentration and their equations were y=-9.01ln x+74.34(Infected group)and y=-4.81ln x+65.15(Healthy group), while the equations between the plasma protein binding rates and free concentration of the drug were y=-6.36ln x+64.91(Infected group) and y=-4.36ln x+ 60.63(Healthy group) in these two groups. Meanwhile the concentration time curve of the two groups were all in accordance with the two-compartment open model. The absorptions and eliminations of DIF in infection group were slower while its apparent distribution volumes and the area under the concentration-time curves were greater than that of the healthy group. The results indicate that the values of the plasma protein binding rates of DIF could be increased by Aeromonas hydrophila in crucian carp, and this may be one of the reasons that leads to limit distribution of drugs, elimination of slowing down and a long stay in the blood in crucian carp which infected by Aeromonas hydrophila.