Clinical pharmacokinetics of dexketoprofen

Clin Pharmacokinet. 2001;40(4):245-62. doi: 10.2165/00003088-200140040-00002.

Abstract

Dexketoprofen trometamol is a water-soluble salt of the dextrorotatory enantiomer of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen. Racemic ketoprofen is used as an analgesic and an anti-inflammatory agent, and is one of the most potent in vitro inhibitors of prostaglandin synthesis. This effect is due to the (S)-(+)-enantiomer (dexketoprofen), while the (R)-(-)-enantiomer is devoid of such activity. The racemic ketoprofen exhibits little stereoselectivity in its pharmacokinetics. Relative bioavailability of oral dexketoprofen (12.5 and 25mg, respectively) is similar to that of oral racemic ketoprofen (25 and 50mg, respectively), as measured in all cases by the area under the concentration-time curve values for (S)-(+)-ketoprofen. Dexketoprofen trometamol, given as a tablet, is rapidly absorbed, with a time to maximum plasma concentration (tmax) of between 0.25 and 0.75 hours, whereas the tmax for the (S)-(+)-enantiomer after the racemic drug, administered as tablets or capsules prepared with the free acid, is between 0.5 and 3 hours. The drug does not accumulate significantly when administered as 25mg of free acid 3 times daily. The profile of absorption is changed when dexketoprofen is ingested with food, reducing both the rate of absorption (tmax) and the maximal plasma concentration. Dexketoprofen is strongly bound to plasma proteins, particularly albumin. The disposition of ketoprofen in synovial fluid does not appear to be stereoselective. Dexketoprofen trometamol is not involved in the accumulation of xenobiotics in fat tissues. It is eliminated following extensive biotransformation to inactive glucuroconjugated metabolites. No (R)-(-)-ketoprofen is found in the urine after administration of dexketoprofen, confirming the absence of bioinversion of the (S)-(+)-enantiomer in humans. Conjugates are excreted in urine, and virtually no drug is eliminated unchanged. The analgesic efficacy of the oral pure (S)-(+)-enantiomer is roughly similar to that observed after double dosages of the racemic compound. At doses above 7mg, dexketoprofen was significantly superior to placebo in patients with moderate to severe pain. A dose-response relationship between 12.5 and 25mg could be seen in the time-effects curves, the superiority of the 25mg dose being more a result of an extended duration of action than of an increase in peak analgesic effect. A plateau in the analgesic activity of dexketoprofen trometamol at the 25mg dose is suggested. The time to onset of pain relief appeared to be shorter in patients treated with dexketoprofen trometamol. The drug was well tolerated.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biotransformation
  • Humans
  • Ketoprofen / pharmacokinetics*
  • Ketoprofen / therapeutic use
  • Stereoisomerism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Ketoprofen