Pharmacodynamic Activity (Leukopoietic Effect) of Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) after Rectal Administration in Rabbits with Leukopenia Induced by Cyclophosphamide

摘要

The pharmacodynamic activity (leukopoietic effect) and pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administered in various doses as hollow-type suppositories were investigated in rabbits with leukopenia induced by cyclophosphamide (CPA-treated rabbits). We found that serum granulocyte colony-stimulating factor (G-CSF) concentration was increased following the rectal administration of rhG-CSF. Therefore, rhG-CSF could be absorbed from the rectal mucosa in leukopenic rabbits who received CPA at a dose of 30mg/kg/d. When rhG-CSF of at least 300/ig/kg was administered rectally once a day for 3d in CPA-treated rabbits I d after the induction of leukopenia (the total count of leukocytes in peripheral blood [total blood leukocyte count] was below 5000/^1), decreased total blood leukocyte count returned to the normal physiological level and a maximum (7000—16000///1) was obtained 3 d after the start of the rhG-CSF multiple-dosing regimen. We report for the first time that rhG-CSF administered rectally induces leukopoiesis in CPA-treated rabbits and reduces the period of leukopenia induced by CPA. Thus, the rhG-CSF hollow-type suppository offers a promising means of reducing the risk of leukopenia, an adverse side effect of CPA therapy.