Chronopharmacology of granulocyte colony-stimulating factor in mice

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 285; no. 1; p. 242
• Main Authors: Ohdo, S, Arata, N, Furukubo, T, Yukawa, E, Higuchi, S, Nakano, S, Ogawa, N
• Format: Journal Article
• Language: English
• Published: United States 01-04-1998
• Subjects: Animals; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Circadian Rhythm - drug effects; Colony-Forming Units Assay; Dose-Response Relationship, Drug; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - metabolism; Granulocyte Colony-Stimulating Factor - pharmacokinetics; Granulocyte Colony-Stimulating Factor - pharmacology; Leukocyte Count - drug effects; Male; Mice; Mice, Inbred ICR
• ISSN: 0022-3565

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 microg/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 microg/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 microg/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.