Chronopharmacology of granulocyte colony-stimulating factor in mice

Shigehiro Ohdo, Naoko Arata, Taku Furukubo, Eiji Yukawa, Shun Higuchi, Shigeyuki Nakano, Nobuya Ogawa

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Abstract

The role of the sensitivity of bone marrow cells to, and the pharmacokinetics of granulocyte colony-stimulating factor (G-CSF) on the rhythm of leukocyte-increasing effect was investigated in ICR male mice housed under a standardized light-dark cycle (lights on at 0700, off at 1900). A significant circadian rhythm was demonstrated for leukocyte counts at 24 hr after G-CSF (250 μg/kg, s.c.) injection at six different circadian times (P < .01). The leukocyte counts of mice given G-CSF at 0500, 0900, 1300 or 1700 were significantly higher than those of mice given G-CSF at 2100 (P < .01, respectively). The rhythmic pattern resembled overall the rhythm occurring after saline injection. In the comparison between leukocyte counts after G-CSF injection at 0700 and 1900, the time when leukocyte counts are equal in nondrugged state, the leukocyte counts at 24 hr after G-CSF (250 μg/kg, i.v.) injection were approximately 50% higher in mice injected with the drug at 0700 than at 1900 (P < .01). Bone marrow cultures obtained at two times of day resulted in different numbers of myeloid colonies even when treated with the same concentrations of G-CSF in vitro. The colony-forming activity of G-CSF was significantly more potent at 0700 than at 1900 (P < .01). The plasma G-CSF concentrations after G-CSF (250 or 5 μg/kg, i.v.) injection were significantly higher in mice receiving injections with the drug at 0700 than at 1900 (P < .05, respectively). The area under the curve and mean residence time were significantly larger in mice injected with the drug at 0700 than at 1900 (P < .01, P < .05, respectively). Our suggests that the rhythm of G-CSF activity is caused by that of the sensitivity of bone marrow cells to, and the pharmacokinetics of the drug.

Original languageEnglish
Pages (from-to)242-246
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume285
Issue number1
Publication statusPublished - Apr 1 1998

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Granulocyte Colony-Stimulating Factor
Leukocyte Count
Injections
Bone Marrow Cells
Pharmaceutical Preparations
Pharmacokinetics
Inbred ICR Mouse
Photoperiod
Circadian Rhythm
Area Under Curve
Leukocytes
Bone Marrow
Light

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Ohdo, S., Arata, N., Furukubo, T., Yukawa, E., Higuchi, S., Nakano, S., & Ogawa, N. (1998). Chronopharmacology of granulocyte colony-stimulating factor in mice. Journal of Pharmacology and Experimental Therapeutics, 285(1), 242-246.

Chronopharmacology of granulocyte colony-stimulating factor in mice. / Ohdo, Shigehiro; Arata, Naoko; Furukubo, Taku; Yukawa, Eiji; Higuchi, Shun; Nakano, Shigeyuki; Ogawa, Nobuya.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 285, No. 1, 01.04.1998, p. 242-246.

Research output: Contribution to journalArticle

Ohdo, S, Arata, N, Furukubo, T, Yukawa, E, Higuchi, S, Nakano, S & Ogawa, N 1998, 'Chronopharmacology of granulocyte colony-stimulating factor in mice', Journal of Pharmacology and Experimental Therapeutics, vol. 285, no. 1, pp. 242-246.
Ohdo S, Arata N, Furukubo T, Yukawa E, Higuchi S, Nakano S et al. Chronopharmacology of granulocyte colony-stimulating factor in mice. Journal of Pharmacology and Experimental Therapeutics. 1998 Apr 1;285(1):242-246.
Ohdo, Shigehiro ; Arata, Naoko ; Furukubo, Taku ; Yukawa, Eiji ; Higuchi, Shun ; Nakano, Shigeyuki ; Ogawa, Nobuya. / Chronopharmacology of granulocyte colony-stimulating factor in mice. In: Journal of Pharmacology and Experimental Therapeutics. 1998 ; Vol. 285, No. 1. pp. 242-246.
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