A review of the pharmacokinetic and pharmacodynamic factors in the potentiation of the antinociceptive effect of nonsteroidal anti-inflammatory drugs by caffeine.
Caffeine is an effective analgesic adjuvant because it increases the antinociceptive effect of NSAIDs while reducing the probability of side effects. The mechanism by which caffeine increases the antinociceptive action of NSAIDs does not appear to include a pharmacokinetic interaction. The potentiation appears to be due to a pharmacokinetic mechanism including actions at the central and the peripheral levels. Because caffeine shifts the effect-compartment concentration-effect relation of NSAIDs to the left and this relationship is sigmoidal, there is no potentiation if the NSAID concentrations are too high or too low with respect to EC(50). The best potentiation can be observed if the NSAID doses used yield effect-compartment concentrations in the vicinity of EC(50). Therefore further investigation of the PK/PD relations of caffeine-NSAID combinations for different pain states and intensities is needed to optimize the therapeutic use of these mixtures.
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico. vgranados@prodigy.net.mx
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Granados-Soto
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Castañeda-Hernández
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans
D000894:Anti-Inflammatory Agents, Non-Steroidal; C016276:8-bromocyclic GMP; D002110:Caffeine; D006152:Cyclic GMP