INFLUENCE OF DOSING TIME ON PHARMACOLOGICAL ACTION OF G-CSF IN MICE

The role of the susceptibility of living organisms and the pharmacokin etics of G-CSF on the rhythm of granulocyte colony-stimulating factor (G-CSF) activity was in investigated. ICR male mice were housed in a s tandardized light-dark cycle (lights on at 0700, off at 1900) with foo d and water ad libitum. The leukocyte counts at 2 and 24 hr after G-CS F (250 mu g/kg, iv) injection were significantly higher in mice inject ed with the drug at 0700 than at 1900 (p < 0.01, respectively). The hi gher leukocyte-increasing effect corresponded to drug dosing at the ti me in which the granulocyte colony formation stimulated by G-CSF and D NA synthesis increased and the lower effect corresponded to drug dosin g at the time in which they decreased. The rhythmicity corresponded to that in plasma G-CSF concentration. The present study suggests that t he rhythm of G-CSF activity is caused by that of the sensitivity of bo ne marrow cells to the drug and the pharmacokinetics of the drug. (C) 1998 Elsevier Science Inc.