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Stereoselective protein binding of ketoprofen: Effect of albumin concentration and of the biological system
Author(s) -
Dubois Nathalie,
Lapicque Françloise,
Abiteboul Michel,
Netter Patrick
Publication year - 1993
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530050305
Subject(s) - chemistry , ketoprofen , enantiomer , human serum albumin , chromatography , stereoselectivity , albumin , serum albumin , enantioselective synthesis , racemic mixture , blood proteins , plasma protein binding , stereochemistry , organic chemistry , biochemistry , catalysis
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. © 1993 Wiley‐Liss, Inc.