The influence of dosing time on the fever induced by interferon-α: (IFN-α) 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-α (10 MIU/kg, i.v.) injection. The rhythmic pattern resembled overall the rhythm occuring in the nondrugged state. IFN-α increased rectal temperature during the light phase, but not during the dark phase. The fever induced by IFN-α was blocked by indomethacin (10 mg/kg, i.p.) pretreatment. There was no significant difference of plasma IFN-α concentrations at 0.167, 0.5 and 1 hr after IFN-α injection. Therefore the dosing time dependent difference of fever induced by IFN-α may be caused via that of PGE2 level elevated by IFN-α. The choice of the most appropriate time of day for drug administration may help to achieve rational chronotherapeutics of IFN- α.
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