Circadian rhythm of fever induced by interferon-alpha in mice.
The influence of dosing time on the fever induced by interferon-alpha (IFN-alpha) was investigated in ICR male mice under light-dark cycle. There was a significant circadian rhythm in rectal temperature, as an index of fever, at 1 hr after IFN-alpha (10 MIU/kg, i.v.) injection. The rhythmic pattern resembled overall the rhythm occurring in the nondrugged state. IFN-alpha increased rectal temperature during the light phase, but not during the dark phase. The fever induced by IFN-alpha was blocked by indomethacin (10 mg/kg, i.p.) pretreatment. There was no significant difference of plasma IFN-alpha concentrations at 0.167, 0.5 and 1 hr after IFN-alpha injection. Therefore the dosing time dependent difference of fever induced by IFN-alpha may be caused via that of PGE2 level elevated by IFN-alpha. The choice of the most appropriate time of day for drug administration may help to achieve rational chronotherapeutics of IFN-alpha.
Ohdo
S
S
Department of Clinical Pharmacokinetics, Kyushu University, Fukuoka, Japan.
Koyanagi
S
S
Yukawa
E
E
Higuchi
S
S
D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D000818:Animals; D002940:Circadian Rhythm; D005334:Fever / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D007213:Indomethacin / Q000627:therapeutic use; D016898:Interferon-alpha / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D018712:Analgesics, Non-Narcotic; D016898:Interferon-alpha; D007213:Indomethacin