CHRONOPHARMACOLOGICAL STUDY OF KE-SI-TO IN MICE

Influence of dosing time on pharmacological effects and toxicity of KE -SI-TO (KST), analgesic and antipyretic drug, was investigated in ICR male mice under LD (12:12) cycle. Significant circadian rhythms were d emonstrated for analgesic and hypothermal effects of KST (1 g/kg, i.p. ) with higher values in the dark and lower ones in the light (p < 0.01 , respectively). The rhythmic patterns of KST-induced analgesia and hy pothermia resembled overall the rhythms occuring in the nondrugged sta te. Injection of KST resulted in a parallel increasing in latency to h ot plate and a parallel decreasing in rectal temperature. KST (6 g/kg, i.p.)induced toxicity also showed a significant circadian rhythm with the highest mortality at 1700 and the lowest one at 0500 (p < 0.05). The principles and concepts of biological rhythm should be included in the consideration of the actions of KST.