PHARMACODYNAMIC ACTIVITY (LEUKOPOIETIC EFFECT) OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (RHG-CSF) AFTER RECTAL ADMINISTRATION IN RABBITS WITH LEUKOPENIA INDUCED BY CYCLOPHOSPHAMIDE

The pharmacodynamic activity (leukopoietic effect) and pharmacokinetic s of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administered in various doses as hollow-type suppositories were inves tigated in rabbits with leukopenia induced by cyclophosphamide (CPA-tr eated rabbits), We found that. serum granulocyte colony-stimulating fa ctor (G-CSF) concentration was increased following the rectal administ ration of rhG-CSF. Therefore, rhG-CSF could be absorbed from the recta l mucosa in leukopenic rabbits mho received CPA at a dose of 30 mg/kg/ d. When rhG-CSF of at least 300 mu g/kg was administered rectally once a day for 3 d in CPA-treated rabbits 1 d after the induction of leuko penia (the total count of leukocytes in peripheral blood [total blood leukocyte count] was below 5000/mu l), decreased total blood leukocyte count returned to the normal physiological level and a maximum (7000- 16000/mu l) mas obtained 3 d after the start of the rhG-CSF multiple-d osing regimen, We report for the first time that rhG-CSF administered rectally induces leukopoiesis in CPA-treated rabbits and reduces the p eriod of leukopenia induced by CPA. Thus, the rhG-CSF hollow-type supp ository offers a promising means of reducing the risk of leukopenia, a n adverse side effect of CPA therapy.