Chronopharmacological study of acetylsalicylic acid in mice.

Influence of dosing time on pharmacological effects and toxicity of acetylsalicylic acid was investigated in ICR male mice under light-dark (12:12) cycle. Significant circadian rhythms (day-night rhythms) were demonstrated for hypothermal and analgesic effects at 1 h after an injection of acetylsalicylic acid (200 mg/kg, i.p.) (P < 0.01, respectively). The rhythmic patterns of acetylsalicylic acid induced analgesia and hypothermia resembled overall the rhythms occurring in the non-drugged state. Injection of acetylsalicylic acid resulted in a parallel increase in latency to hot plate and a parallel decrease in rectal temperature. The relationship between plasma salicylate concentrations and responses was not clear. There was also a significant circadian rhythm in acetylsalicylic acid (850 mg/kg, i.p.) induced toxicity with the highest mortality at 17:00 and the lowest one at 05:00 (P < 0.05). Dosing time dependent kinetics of salicylate seems to be related to the rhythm of toxicity of the drug. The time in circadian stage at which acetylsalicylic acid is administered is essentially important in the actions of acetylsalicylic acid.