title: Pharmacodynamic activity (leukopoietic effect) of recombinant human granulocyte colony-stimulating factor (rhG-CSF) after rectal administration in rabbits with leukopenia induced by cyclophosphamide.
abstract: 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 30 mg/kg/d. When rhG-CSF of at least 300 micrograms/kg was administered rectally once a day for 3 d in CPA-treated rabbits 1 d after the induction of leukopenia (the total count of leukocytes in peripheral blood [total blood leukocyte count] was below 5000/microliter), decreased total blood leukocyte count returned to the normal physiological level and a maximum (7000-16000/microliter) 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.
authors.affiliation: Department of Pharmaceutics, Showa College of Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Kiriyama
authors.forename: J
authors.initials: J
authors.lastname: Oe
authors.forename: R
authors.initials: R
authors.lastname: Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Mizufune
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D003520:Cyclophosphamide; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D007970:Leukopenia / Q000188:drug therapy*; D008297:Male; D011817:Rabbits; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide