Stereoselective binding of the glucuronide conjugates of carprofen enantiomers to human serum albumin.
The stereoselective binding of carprofen enantiomers and carprofen glucuronide diastereomers to human serum albumin (HSA) was studied using an ultrafiltration method. Carprofen glucuronides exhibit a considerable and stereoselective affinity to HSA, although less than that seen for the parent enantiomers. The (S)-glucuronide showed a higher binding affinity to HSA than the (R)-glucuronide. The (S)-enantiomer of unmetabolized carprofen was bound to fatty acid free HSA to a much greater extent than the (R)-enantiomer. Warfarin reduced the binding of the glucuronides to a greater extent than did diazepam, but diazepam displaced the unconjugated enantiomers to a greater extent than did warfarin. These results suggest differences in binding region between the carprofen enantiomers and their glucuronides on the albumin molecule.
Iwakawa
S
S
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
Spahn
H
H
Benet
L Z
LZ
Lin
E T
ET
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D001665:Binding Sites; D002227:Carbazoles / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism*; D006801:Humans; D012709:Serum Albumin / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014462:Ultrafiltration
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D005965:Glucuronates; D012709:Serum Albumin; C007005:carprofen