title: Stereoselective binding of the glucuronide conjugates of carprofen enantiomers to human serum albumin.
abstract: 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.
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
authors.forename: S
authors.initials: S
authors.lastname: Iwakawa
authors.forename: H
authors.initials: H
authors.lastname: Spahn
authors.forename: L Z
authors.initials: LZ
authors.lastname: Benet
authors.forename: E T
authors.initials: ET
authors.lastname: Lin
mesh_terms: 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
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D005965:Glucuronates; D012709:Serum Albumin; C007005:carprofen