CHRONOPHARMACOLOGICAL STUDY OF ACETYLSALICYLIC-ACID IN MICE

Influence of dosing time on pharmacological effects and toxicity of ac etylsalicylic 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 inj ection of acetylsalicylic acid (200 mg/kg, i.p.) (P < 0.01, respective ly). The rhythmic patterns of acetylsalicylic acid induced analgesia a nd hypothermia resembled overall the rhythms occurring in the non-drug ged state. Injection of acetylsalicylic acid resulted in a parallel in crease in latency to hot plate and a parallel decrease in rectal tempe rature. 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 h ighest mortality at 17:00 and the lowest one at 05:00 (P < 0.05). Dosi ng time dependent kinetics of salicylate seems to be related to the rh ythm of toxicity of the drug. The time in circadian stage at which ace tylsalicylic acid is administered is essentially important in the acti ons of acetylsalicylic acid.