Stereoselective pharmacokinetics and inversion of (R)- ketoprofen in healthy volunteers

J Clin Pharmacol. 1998 Feb;38(2S):3S-10S. doi: 10.1002/j.1552-4604.1998.tb04411.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / blood
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / urine
  • Cyclooxygenase Inhibitors / blood
  • Cyclooxygenase Inhibitors / pharmacokinetics*
  • Cyclooxygenase Inhibitors / urine
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Ketoprofen / blood
  • Ketoprofen / pharmacokinetics*
  • Ketoprofen / urine
  • Male
  • Stereoisomerism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Ketoprofen