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.
Department of Pharmacobiology, CINVESTAV-IPN, Mexico DF, Mexico. flopezm@prodigy.net.mx
F J
FJ
López-Muñoz
R
R
Ventura
M I
MI
Díaz
G P
GP
Hernández
A M
AM
Domínguez
M L
ML
García
F
F
Cabré
D
D
Mauleón
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001168:Arthritis / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005480:Flurbiprofen / Q000031:analogs & derivatives / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010003:Osteoarthritis / Q000188:drug therapy; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014527:Uric Acid
D000700:Analgesics; D014527:Uric Acid; D005480:Flurbiprofen