Determination of the optimal analgesia-potentiating dose of caffeine and a study of its effect on the pharmacokinetics of aspirin in mice.

The addition of caffeine 10 mg/kg to analgin, paracetamol and aspirin increased the potency of the combination compared to that of the analgesic used alone, giving a potency ratio of 1.58, 2.5 and 3.23, respectively as assayed by the writhing method in mice. Increasing the dose of caffeine further reduced the potency of the combination so that with 100 mg/kg caffeine the potency ratio for the combination against the analgesic alone was analgin 1.25, paracetamol 0.94 and aspirin 0.88. The Cmax, Tmax, t1/2 and AUC of plasma salicylate was not significantly different when aspirin 65 mg/kg was given alone or in combination with caffeine 10 mg/kg p.o. in mice. Therefore, caffeine is maximally effective in potentiating the effect of analgesics at a dose of 10 mg/kg and this potentiation is not due to a pharmacokinetic interaction with the analgesic, and also not due to phosphodiesterase (PDE) inhibition.