目的:探讨头孢哌酮(CPZ)、乳酸环丙沙星(CFLX)单独和同时存在时与人血清白蛋白(HSA)的相互作用。方法:采用荧光光谱法研究CPZ、CFLx单独和同时存在时对HSA的荧光猝灭作用,通过Stern—Volmer方程计算猝灭常数(Kq),判断猝灭机制;计算结合常数(缸)和结合位点数。结果:20、37℃时,HSA.CPZ体系的凰分别为1.1×10^12、0.87×10^12L/(mol·s);HSA.CFLX体系K分别为2.67×10^12、1.75×10^12L/(mol·s)。CPZ和CFLX对HSA的内源性荧光均因形成复合物而产生静态猝灭。20、37℃时HSA—CPZ和HSA—CFLX体系的以为0.11×10^3~1.79×10^3L/mol,结合位点数为0.57~0.75。37℃时,HSA—CFLX.CPZ体系的乜值为3.47×10^3L/mol,与HSA—CPZ体系心值之比为31.55;HSA—CPZ—CFLX体系的凡值为3.59×10^3L/mol,与HSA.CFLX体系心值之比为8.55。结论:CPZ和CFLX同时存在时,一种药物的存在会使另外一种药物与HSA的心增大、结合稳定性增强,从而致使游离药物的浓度降低,药效下降。
OBJECTIVE: To investigate the interaction of cefoperazone (CPZ) and ciprofloxacin lactate (CFLX) alone or com- bination with human serum albumin (HSA). METHODS: Fluorescence spectrum was used to investigate the fluorescence quench- ing effect of CPZ and CFLX alone or combination on HSA. The quenching constants (Kq) were calculated by using Stern-Volmer equation to determine quenching mechanism, and the binding constant (KA) and the number of binding site were obtained. RE- SULTS: At 20 ℃ and 37 ℃, Kq of HSA-CPZ were 1.1×10^12, 0.87×10^12 L/(mol-s); Kq of HSA-CFLX were 2.67×10^12, 1.75×10^2 L/(mol-s). CPZ and CFLX could cause the static quenching of HSA endogenous fluorescence due to forming compound. At 20 ℃ and 37 ℃, KA of HSA-CPZ and HSA-CFLX were 0.11×10^3-1.79×10^3 L/mol and binding sites of them were 0.57-0.75. At 37 ℃, KA of HSA-CFLX-CPZ was 3.47×10^3 L/mol, and ratio of it to KA of HSA-CPZ was 31.55; KA of HSA-CPZ-CFLX was 3.59×10^3 L/mol, and ratio of it to KA of HSA-CFLX was 8.55. CONCLUSIONS: CPZ and CFLX in the ternary system, the presence of one drug would enhance the binding constant and stability of the other drug with HSA, which induces the concentration of free drug decreasing and the efficacy of the drugs could be reduced.