Influence of dosing time on pharmacological action of G-CSF in mice.
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 microg/kg, i.v.) 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.
Ohdo
S
S
Department of Clinical Pharmacokinetics, Kyushu University, Fukuoka, Japan.
Furukubo
T
T
Arata
N
N
Yukawa
E
E
Higuchi
S
S
Nakano
S
S
Ogawa
N
N
D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004334:Drug Administration Schedule; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D016179:Granulocyte Colony-Stimulating Factor