Influence of dosing time on pharmacological action of G-CSF in mice

• Published in: Life sciences (1973) Vol. 62; no. 12; pp. PL163 - PL168
• Main Authors: Ohdo, Shigehiro, Furukubo, Taku, Arata, Naoko, Yukawa, Eiji, Higuchi, Shun, Nakano, Shigeyuki, Ogawa, Nobuya
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 1998
• Subjects: Animals; cell cycle; chronopharmacology; circadian rhythm; Circadian Rhythm - physiology; Drug Administration Schedule; G-CSF; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - pharmacokinetics; Granulocyte Colony-Stimulating Factor - pharmacology; Leukocyte Count - drug effects; Male; Mice; Mice, Inbred ICR; chronopharmacology; cell cycle; G-CSF; circadian rhythm
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(98)00038-1

The role of the susceptibility of living organisms and the pharmacokinetics of G-CSF on the rhythm of granulocyte colony-stimulating factor (G-CSF) activity was investigated. ICR male mice were housed in a standardized light-dark cycle (lights on at 0700, off at 1900) with food and water ad libitum. The leukocyte counts at 2 and 24 hr after G-CSF (250 μg/kg, iv) injection were significantly higher in mice injected with the drug at 0700 than at 1900 (p > 0.01, respectively). The higher leukocyte-increasing effect corresponded to drug dosing at the time in which the granulocyte colony formation stimulated by G-CSF and DNA synthesis increased and the lower effect corresponded to drug dosing at the time in which they decreased. The rhythmicity corresponded to that in plasma G-CSF concentration. The present study suggests that the rhythm of G-CSF activity is caused by that of the sensitivity of bone marrow cells to the drug and the pharmacokinetics of the drug.