Potentiation of the Analgesic Effect of Tolmetin, a Potent Non-steroidal Anti-inflammatory Drug, by Caffeine in the Rat

Abstract

The analgesic activities of tolmetin (0, 3, 10 and 32 mg kg−1), caffeine (0, 10, 18, 32 and 56 mg kg−1) and combinations of these doses were studied in the pain-induced functional impairment model in the rat. Tolmetin was able to produce a dose-dependent analgesic effect, whereas caffeine was ineffective in this model; 3–32, 3–56 and 10–56 mg kg−1 tolmetin-caffeine, but not other combinations, yielded analgesic effects which were significantly greater than those observed with tolmetin alone. However, tolmetin pharmacokinetics were not modified by caffeine co-administration. The results show that caffeine is able to potentiate the analgesic activity of tolmetin, probably by a pharmacodynamic mechanism of action, but only at selected dose combinations.