Stereoselective serum protein binding of ketoprofen in liver diseases.
The stereoselective binding of ketoprofen (KP) to human serum was studied in patients with liver diseases and was compared with that of normal volunteers. The serum protein binding of racemic KP was found to be decreased in hepatic patients whereas, interestingly, the stereoselectivity of KP was increased. The ratio of unbound concentrations of the KP enantiomers (FR/FS) showed positive linear correlation with albumin concentrations. Inhibition of KP binding to human serum albumin (HSA) induced by lithocholate, lithocholate sulfate and bilirubin was studied. The data presented in this paper strongly suggest that the variation of stereoselective binding of KP in patients suffering from liver diseases was mainly caused by the decrease of HSA levels and secondly by the stereoselective inhibition induced by the increased concentrations of bile acid and its metabolite.
Sakai
T
T
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Maruyama
T
T
Sako
T
T
Ahmed
S
S
Zuidema
X
X
Fujiyama
S
S
Otagiri
M
M
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism*; D001806:Blood Urea Nitrogen; D003401:Creatine / Q000097:blood; D005260:Female; D006801:Humans; D007660:Ketoprofen / Q000097:blood* / Q000737:chemistry*; D007700:Kinetics; D008103:Liver Cirrhosis / Q000097:blood; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012016:Reference Values; D012044:Regression Analysis; D012709:Serum Albumin / Q000378:metabolism; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001647:Bile Acids and Salts; D001798:Blood Proteins; D012709:Serum Albumin; D007660:Ketoprofen; D003401:Creatine