Increase in total blood leukocyte count following intranasal administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits with cyclophosphamide-induced leukopenia.

We investigated the effects of intranasal (i.n.) administration of recombinant human granulocyte colony-stimulating factors (rhG-CSF) on the total count of leukocytes in peripheral blood (total blood leukocyte count) of rabbits with leukopenia who received cyclophosphamide (CPA). When CPA (30 mg/kg per d) was administered intravenously, the total blood leukocyte count decreased to levels below 5000/microliters approximately 4 d after the initiation of CPA multiple dosing. The decreased level of the total blood leukocyte count was maintained throughout the period of CPA dosing. RhG-CSF was given once a day for 3 d in CPA-treated rabbits via i.n. administration of aqueous preparations containing rhG-CSF with or without alpha-cyclodextrin (alpha-CyD). The total blood leukocyte count increased from levels below 5000/microliters to the normal physiological level following i.n. administration of rhG-CSF preparation and reduced the period of leukopenia induced by CPA. The coadministration of rhG-CSF and alpha-CyD was more effective in increasing the total blood leukocyte count. It is suggested that i.n. administration of rhG-CSF is promising for reducing the risk of cytotoxic chemotherapy (CPA)-induced leukopenia as an adverse side effect.