A review of the pharmacokinetic and pharmacodynamic factors in the potentiation of the antinociceptive effect of nonsteroidal anti-inflammatory drugsby caffeine

Caffeine is an effective analgesic adjuvant because it increases the antino ciceptive effect of NSAIDs while reducing the probability of side effects. The mechanism by which caffeine increases the antinociceptive action of NSA IDs does not appear to include a pharmacokinetic interaction. The potentiat ion appears to be due to a pharmacokinetic mechanism including actions at t he central and the peripheral levels. Because caffeine shifts the effect-co mpartment concentration-effect relation of NSAIDs to the left and this rela tionship is sigmoidal, there is no potentiation if the NSAID concentrations are too high or too low with respect to EC50. The best potentiation can be observed if the NSAID doses used yield effect-compartment concentrations i n the vicinity of EC50. Therefore further investigation of the PK/PD relati ons of caffeine-NSAID combinations for different pain states and intensitie s is needed to optimize the therapeutic use of these mixtures. (C) 2000 Els evier Science Inc. All rights reserved.