Pharmacokinetics of ketoprofen enantiomers in young and elderly arthritic patients following single and multiple doses

J Pharm Sci. 1988 Mar;77(3):191-5. doi: 10.1002/jps.2600770302.

Abstract

Ketoprofen (KT), a chiral nonsteroidal anti-inflammatory drug (NSAID), is marketed and used as a racemic mixture. In healthy volunteers, negligible differences have been reported between the plasma time courses of KT enantiomers. Using a stereospecific high-performance liquid chromatographic (HPLC) assay measuring (R)- and (S)-KT in plasma and urine, pharmacokinetics of the enantiomers following single (50 mg) and then multiple (50 mg every 6 h for 3 d) doses were delineated in nine young and nine elderly arthritic patients. There were no significant differences between pharmacokinetic indices calculated after single and multiple doses, or between the two groups. In plasma, there were no significant differences between intact enantiomers in either patient group. However, significantly more conjugated (S)-KT was found in elderly patient plasma. Similar to findings in healthy volunteers, elimination of conjugated KT in both patient groups was more extensive for the (S)-, as compared with the (R)-isomer. It is suggested that age-dependent impaired elimination of conjugated (S)-KT, along with preferential biliary excretion of conjugated (R)-KT, is responsible for these observations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / metabolism
  • Arthritis / metabolism*
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Ketoprofen / administration & dosage
  • Ketoprofen / pharmacokinetics*
  • Male
  • Middle Aged
  • Phenylpropionates / pharmacokinetics*
  • Stereoisomerism

Substances

  • Phenylpropionates
  • Ketoprofen