Basis for dosing time-dependent changes in the antiviral activity of interferon-α in mice

Shigehiro Ohdo, De Sheng Wang, Koyanagi Satoru, Hiroshi Takane, Kouichi Inoue, Hironori Aramaki, Eiji Yukawa, Shun Higuchi

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Abstract

The influence of dosing time on the pharmacological effect (antiviral activity) of interferon-α (IFN-α), and the pharmacological and pharmacokinetic mechanisms, were investigated in ICR male mice under a 12-h light/dark cycle (lights on from 7:00 AM to 7:00 PM). 2'-5'Oligoadenylate synthetase activity in plasma at 24 h after IFN-α (10 MI.U./kg, i.v.) injection, as an index of antiviral activity, was significantly higher for injections given at 9:00 AM than for injections given at 9:00 PM (P < .05). The uptake of [3H]thymidine by lymphocytes after 24-h incubation with IFN- α, as an index of lymphocyte-stimulating effect, was significantly higher in cells obtained at 9:00 AM than in the cells obtained at 9:00 PM (P < .01). The number of receptors per cell and the expression of interferon-stimulated gene factor in lymphocytes after 24-h incubation with IFN-α were significantly higher in the cells obtained at 9:00 AM than at 9:00 PM (P < .05). A significant dosing time-dependent difference was demonstrated for the pharmacokinetic parameters of IFN-α, which showed higher clearance for injections given at 9:00 PM than for those at 9:00 AM (P < .05). The metabolism of IFN-α was significantly higher in kidney obtained at 9:00 PM than at 9:00 AM (P < .05). These findings support that choosing the most appropriate time of day for administration of IFN-α, associated with the rhythmicity of IFN-α receptor function and IFN-α pharmacokinetics, may increase the antiviral activity in experimental and clinical situations.

Original languageEnglish
Pages (from-to)488-493
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume294
Issue number2
Publication statusPublished - Aug 1 2000

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Interferons
Antiviral Agents
Injections
Pharmacokinetics
Lymphocytes
Interferon Receptors
Pharmacology
Inbred ICR Mouse
Photoperiod
Periodicity
Ligases
Thymidine
Kidney
Light
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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Basis for dosing time-dependent changes in the antiviral activity of interferon-α in mice. / Ohdo, Shigehiro; Wang, De Sheng; Satoru, Koyanagi; Takane, Hiroshi; Inoue, Kouichi; Aramaki, Hironori; Yukawa, Eiji; Higuchi, Shun.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 294, No. 2, 01.08.2000, p. 488-493.

Research output: Contribution to journalArticle

Ohdo, S, Wang, DS, Satoru, K, Takane, H, Inoue, K, Aramaki, H, Yukawa, E & Higuchi, S 2000, 'Basis for dosing time-dependent changes in the antiviral activity of interferon-α in mice', Journal of Pharmacology and Experimental Therapeutics, vol. 294, no. 2, pp. 488-493.
Ohdo, Shigehiro ; Wang, De Sheng ; Satoru, Koyanagi ; Takane, Hiroshi ; Inoue, Kouichi ; Aramaki, Hironori ; Yukawa, Eiji ; Higuchi, Shun. / Basis for dosing time-dependent changes in the antiviral activity of interferon-α in mice. In: Journal of Pharmacology and Experimental Therapeutics. 2000 ; Vol. 294, No. 2. pp. 488-493.
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