双氟沙星与异育银鲫血浆蛋白的结合率

为了研究双氟沙星(difloxacin,DIF)与异育银鲫(Carassais auratus gibebio)血浆蛋白的结合性质,采用平衡透析法测定了DIF与异育银鲫血浆蛋白的体外结合率,并研究了温度、血浆浓度及药物浓度对其的影响。结果显示:DIF血浆蛋白结合率在4℃、15℃、20℃、25℃、30℃、37℃条件下变化差异不显著(P>0.05);药物血浆蛋白结合率显著高于二倍稀释血浆的结合率,也显著高于四倍稀释血浆的结合率(P<0.05)。当DIF浓度在0.5～5μg/mL范围之间时,药物与血浆蛋白结合率在32.4%～19.6%之间,并随着药物浓度的升高而降低,最大结合能力(β)和解离常数(Kdp)分别为3.5×10-7 mol/g和4.04×10-6 mol/L;当DIF质量浓度为5～40μg/mL范围内时,血浆蛋白结合率的变化差异不显著(P>0.05)。此外,游离药物与总药物浓度呈线性关系,关系式为y=0.77x-0.18。结果表明,DIF与异育银鲫血浆蛋白结合率在本实验条件下不受温度影响,且具有浓度依赖性;在0.5～5μg/mL范围内结合率为非线性,而在5～40μg/mL范围内为线性。本研究旨在为DIF药物代谢动力学理论研究及其临床用药提供理论参考。

Plasma protein binding rate of difloxacin in crucian carp Carassais auratus gibelio

Equilibrium dialysis was used to determine the in vitro binding rates of difloxacin(DIF) to plasma pro-teins of Carassius auratus gibelio and to investigate the effects of temperature,and of the concentrations of plasma and the drug,on the binding characteristics.The binding rate decreased from 32.4% to 19.6% as the drug concentration was raised from 0.5 μg/mL to 5 μg/mL but was unchanged between drug concentrations of 5μg/mL and 40 μg/mL.The binding rates were not affected by temperatures of 4,15,20,25,or 37℃,but the binding rate in undiluted plasma was significantly higher than in twofold(8.87±0.39)% and fourfold(4.09±0.24)% diluted plasma(P<0.05).The highest combining ability(β) and dissociation constant(Kdp) were 3.5×10-7 mol/g and 4.04×10-6 mol/L,respectively.The concentration of the dissociated drug had a linear relationship with the total concentration of the drug and was given by the equation: y = 0.77x -0.18.Thus,the binding rate of DIF to plasma protein in Carassius auratus gibelio is drug concentration-dependent;it is not affected by experimental tempera-tures between 4℃ and 37℃;it is linear with concentrations of DIF between 5 μg/mL and 40 μg/mL;and it shows a nonlinear relationship between 0.5 μg/mL and 5 μg/mL.