Dubois N, Lapicque F, Abiteboul M, Netter P
Laboratoire de Pharmacologie and URA CNRS 1288, Faculté de Médecine, Vandoeuvre les Nancy, France.
Chirality. 1993;5(3):126-34. doi: 10.1002/chir.530050305.
Equilibrium dialysis was used to study in vitro the enantioselective binding of R, S, and racemic ketoprofen at physiological pH and temperature in human serum albumin (HSA) (1, 20, and 40 g/liter) and in plasma. The binding of enantiomers in a racemic mixture was studied to see the effect of each isomer on the other's interaction with the protein. The free fractions were determined by high-performance liquid chromatography. The binding of ketoprofen enantiomers to albumin was enantioselective, depending on both drug and protein concentrations. Enantioselectivity was observed in plasma too but was the opposite of that in HSA at 40 g/liter. The percentage of each isomer unbound was higher in the racemic mixture than with the isomer alone. The displacement of probes specific for HSA sites I and II, studied by spectrofluorimetry, suggests that all three preparations of ketoprofen are bound mainly to site I and secondarily to site II.
采用平衡透析法在生理pH值和温度条件下，研究了R-、S-和外消旋酮洛芬在人血清白蛋白（HSA，浓度分别为1、20和40 g/L）及血浆中的对映体选择性结合。研究了外消旋混合物中对映体的结合情况，以观察每种异构体对另一种异构体与蛋白质相互作用的影响。通过高效液相色谱法测定游离分数。酮洛芬对映体与白蛋白的结合具有对映体选择性，这取决于药物和蛋白质的浓度。在血浆中也观察到了对映体选择性，但与40 g/L的HSA中的情况相反。外消旋混合物中每种异构体未结合的百分比高于单独异构体的情况。通过荧光光谱法研究了对HSA位点I和II具有特异性的探针的置换情况，结果表明，三种酮洛芬制剂主要结合在位点I，其次结合在位点II。
