Clinical pharmacokinetics of dexketoprofen

Dexketoprofen trometamol is a water-soluble salt of the dextrorotatory enan tiomer of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen. Racem ic ketoprofen is used as an analgesic and an anti-inflammatory agent, and i s one of the most potent in vitro inhibitors of prostaglandin synthesis. Th is 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 pharmacokin etics. Relative bioavailability of oral dexketoprofen (12.5 and 25mg, respe ctively) is similar to that of oral racemic ketoprofen (25 and 50mg, respec tively), as measured in all cases by the area under the concentration-time curve values for (S)(+)-ketoprofen. Dexketoprofen trometamol, given as a ta blet, is rapidly absorbed, with a time to maximum plasma concentration (t(m ax)) of between 0.25 and 0.75 hours, whereas the tmax for the (S)-(+)-enant iomer 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 accumulat e significantly when administered as 25mg of free acid 3 times daily. The p rofile of absorption is changed when dexketoprofen is ingested with food, r educing both the rate of absorption (t(max)) and the maximal plasma concent ration. Dexketoprofen is strongly bound to plasma proteins, particularly albumin. T he disposition of ketoprofen in synovial fluid does not appear to be stereo selective. Dexketoprofen trometamol is not involved in the accumulation of xenobiotics in fat tissues. It is eliminated following extensive biotransfo rmation to inactive glucuroconjugated metabolites. No (R)-(-)-ketoprofen is found in the urine after administration of dexketoprofen, confirming the a bsence 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 simil ar 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 incr ease in peak analgesic effect. A plateau in the analgesic activity of dexke toprofen trometamol at the 25mg dose is suggested. The time to onset of pai n relief appeared to be shorter in patients treated with dexketoprofen trom etamol. The drug was well tolerated.