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 demonstrated 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 hypothermia resembled overall the rhythms occuring in the nondrugged state. Injection of KST resulted in a parallel increasing in latency to hot 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.
Ogawa
N
N
Department of Pharmacology, Ehime University School of Medicine, Onsen-Gun, Japan.
Ohdo
S
S
Song
J G
JG
Higuchi
S
S
D000700:Analgesics / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D001833:Body Temperature Regulation; D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D000700:Analgesics; D018712:Analgesics, Non-Narcotic