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℃、20C、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 ～5 μg/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5～40 μg/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0.5～5 μg/mL范围内结合率为非线性,而在5～40 μg/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.%Equilibrium dialysis was used to determine the in vitro binding rates of difloxacin (DIF) to plasma proteins 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×l0-7 mol/g and 4.04×l0-6 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 = 0.77× - 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 temperatures 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.
展开▼
