Enhancement of (S)-Ketoprofen Antinociception by Caffeine Co-administration: Effects in an Arthritic-Pain Animal Model

To find a possible synergistic antinociceptive interaction, several doses of (S)-ketoprofen and caffeine were administered in an arthritic-pain model. To induce nociception rats were administered intraarticularly with uric acid suspension. Then, animals received p.o. (S)-ketoprofen (0.1-31.6 mg/kg), caffeine (17.8 mg/kg) and the same doses of (S)-ketoprofen plus caffeine. The efficacy and potency were evaluated based on the protocol of PIFIR model. (S)-ketoprofen induced a dose-dependent antinociceptive effect and caffeine alone did not show any effect. ED50 of (S)-ketoprofen alone and with caffeine changed from 3.8 +/- 1.5 to 1.1 +/- 0.1 mg/kg. Additionally, caffeine was able to modify the efficacy of (S)ketoprofen (3.2 mg/kg) moving the value of AUC(0-4) of 121.09 +/- 12.36 to 271.6 +/- 25.24 % h (124% of difference). The results showed the caffeine's capacity to potentiate the antinociceptive effect of (S)-ketoprofen only at selected dose combinations.