Stereoselective pharmacokinetics and inversion of (R)- ketoprofen in healthy volunteers.
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.
Rudy
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AC
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Liu
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Y
Brater
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Hall
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SD
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007660:Ketoprofen