Analysis of antinociceptive effects of flurbiprofen enantiomers in a rat model of arthritic pain.

The potential antinociceptive effects of the S(+)- and R(-)-enantiomers of flurbiprofen (SFB and RFB, respectively) were investigated when given intravenously to rats using the pain-induced functional impairment model in the rat (PIFIR), an animal model of arthritic pain. Groups of 6 rats received either vehicle or the enantiomer in turn and antinociception was determined by evaluating the dose-response curves over time. Although SFB and RFB produced dose-dependent effects with similar efficacy (SFB: 277.4 +/- 29.9 au and RFB: 293.5 +/- 20.1 au), the R(-)-enantiomer was unable to produce any antinociceptive action when assessed at the same dose ranges as SFB. It was necessary to increase the dose of RFB by 100 times to produce similar antinociception. Accordingly, S(+)-flurbiprofen was 100-fold more potent (ED50 = 0.33 +/- 0.13 mg/kg) than its antipode R(-)-(ED50 = 30.0 +/- 1.7 mg/kg). SFB generated from metabolic inversion (> 1%) after i.v. dosage of RFB, as well as impurities of SFB present in RFB preparations, tend to confirm the hypothesis that the efficacy of RFB achieved at 100 mg/kg, similar to that observed with 1 mg/kg of SFB, is attributable to SFB.

Antinociceptive effects of S(+)-ketoprofen and other analgesic drugs in a rat model of pain induced by uric acid.

We investigated the antinociceptive properties of dexketoprofen trometamol [S(+)-ketoprofen tromethamine salt; SKP], a new analgesic, antiinflammatory drug, using the pain-induced functional impairment model in the rat (PIFIR), an animal model of arthritic pain. SKP was compared with racemic ketoprofen tromethamine salt (rac-KP), R(-)-ketoprofen tromethamine salt (RKP), ketorolac (KET), and morphine (MOR). We also assessed the effects of flurbiprofen (rac-FB) and its enantiomers (SFB and RFB) in the same model. Groups of six rats received either vehicle or analgesic drug and antinociception was evaluated by evaluating the dose-response curves over time. SKP was an effective antinociceptive drug in this model and was almost equally potent by either oral or intracerebroventricular administration. The oral potency of SKP was similar to that of oral KET and greater than that of oral MOR. No significant differences were observed between racemic ketoprofen and its enantiomers when administered orally. In the rat, significant bioinversion of RKP to SKP occurs when RKP is given orally. After oral administration of RKP, SKP was detectable in 30 min and surpassed the concentration of RKP after 3 h. Nevertheless, when the compounds were given intracerebroventricularly, some stereoselectivity in favor of SKP was observed. Stereoselectivity was observed with flurbiprofen, an analogue of ketoprofen that does not undergo significant metabolic inversion. Whereas SFB was an effective antinociceptive, RFB had no antinociceptive effect at the doses tested when given either orally or intracerebroventricularly.