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 (F-inv) 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 (C-max) 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 IP < 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.