【摘要】 目的:建立间尼索地平不同对映体在大鼠血浆、人血浆和牛血清白蛋白中蛋白结合率的测定方法,并计算不同种属血浆蛋白的相关参数。方法:采用平衡透析法测定蛋白结合率,用高效液相色谱法测定血浆中药物总浓度及游离药物浓度。结果:R-与S-间尼索地平的血浆蛋白结合率分别为:大鼠血浆为(97.4±8.2)%、(93.0±13.4)%;人血浆为(90.8±10.5)%、(89.2±9.9)%;牛血清白蛋白为(95.3±8.7)%、(91.0±5.7)%。最低定量下限为0.01ng。结论:在体外间尼索地平不同对映体与大鼠血浆、人血浆和牛血清白蛋白结合率很高,R-间尼索地平的结合率及蛋白结合药物的表观最大能力βp均较S-间尼索地平高。随着药物血浆浓度升高,R-间尼索地平结合率下降,S-间尼索地平结合率升高,均有一定的浓度依赖性。更多还原

【Abstract】 OBJECTIVE A HPLC method was established to determine the protein binding rates of m-nisoldipine enantiomers in human plasma,rat plasma,bovine serum albumin(BSA),and to calculative the correlate parameters of m-nisoldipine enantiomers to different genera plasma proteins.METHODS The binding rates of m-nisoldipine enantiomers with different genera plasma proteins were determined by equilibrium dialysis method.The concentrations of m-nisoldipine enantiomers were assayed by HPLC.RESULTS The binding rates of R-,S-m-nisoldipine with rat,human plasma and BSA were(97.4±8.2)%,(93.0±13.4)%;(90.8±10.5)%,(89.2±9.9)% and(95.3±8.7)%,(91.0±5.7)%,respectively.The method was sensitive with a lower limit of quantification of 0.01 ng in different plasma.CONCLUSION The binding rates of m-nisoldipine enantiomers to human plasma protein,rat plasma protein and BSA were very high.The plasma protein binding rate and βp of R-m-nisoldipine was higher than those of S-m-nisoldipine.Moreover the binding rate was inversely proportional to plasma concentration of R-m-nisoldipine,while the S-m-nisoldipine was identical.更多还原