Bioinversion of R(−)-Ketoprofen After Oral Administration in Healthy Volunteers

The extent of bioinversion and recovery of R(−)-ketoprofen in urine after oral administration was investigated in 12 healthy human volunteers. In an open study, subjects received a single oral dose of R(−)-ketoprofen 50mg (free acid without excipients). In the 48 hours after administration, a mean of 48.4% of the administered dose was recovered in the urine as ketoprofen enantiomers (predominantly as the glucuronoconjugated form); considerable intersubject variability was observed (range 6.6 to 66.4%).The vast majority of drug recovered in the urine was excreted in the first 24 hours, principally during the first 6 hours. The mean percentage of S(+)-enantiomer of the total excreted in the cumulative 24-hour period after drug administration ranged from 7.7 to 23.3% (mean 12.7%). At 24 hours, plasma concentrations of R(−)- or S(+)-enantiomers of ketoprofen tended to be below the limit of quantification and consequently it was not possible to calculate the extent of bioinversion of R(−)-ketoprofen to the S(+)-enantiomer in plasma. No clinically relevant changes in vital signs or laboratory parameters were reported. Thus, overall, the results of this study suggest that R(−)-ketoprofen undergoes limited, variable bioinversion to the S(+) antipode in humans. If these findings are confirmed after oral administration of racemic ketoprofen, then a rationale exists for administering the S(+)-enantiomer per se rather than the racemic mixture.