title: Stereoselective pharmacokinetics and inversion of (R)- ketoprofen in healthy volunteers.
abstract: The pharmacokinetics of ketoprofen enantiomers were evaluated after 25-, 50-, and 100-mg doses of (R)- ketoprofen and 100 mg of racemic ketoprofen in 25 healthy volunteers (12 male and 13 female). The fractional inversion (Finv) of (R)- ketoprofen was 8.9 +/- 3.3% using plasma data and 10.0 +/- 2.2% using urine data. There were small (< 5%) but significant differences between the enantiomers for areas under the plasma concentration-time curve (AUC) after the racemic dose (P < 0.005). Half-lives were 130-144 minutes for (R)- ketoprofen and 132-209 minutes for (S)- ketoprofen. Dose proportionality in AUC and maximum plasma concentration (Cmax) values was noted for both enantiomers. A total of 69% of the dose was recovered in the urine as (R)- and (S)- ketoprofen and conjugates. The elimination rate constant of (R)- ketoprofen was significantly different (P < 0.05) between men and women. Exposure to cyclooxygenase inhibiting (S)- ketoprofen was approximately 10% of the dose after the administration of pure (R)- ketoprofen and was independent of gender.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Rudy
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Brater
authors.forename: S D
authors.initials: SD
authors.lastname: Hall
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007660:Ketoprofen / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007660:Ketoprofen