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标题：Pharmacodynamic Activity (Leukopoietic Effect) of Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) after Rectal Administration in Rabbits with Leukopenia Induced by Cyclophosphamide
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作者：Yoshiteru WATANABE ; Miyuki KIRIYAMA ; Junko OE 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1996
卷号：19
期号：8
页码：1064-1067
DOI：10.1248/bpb.19.1064
出版社：The Pharmaceutical Society of Japan
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 30 mg/kg/d. When rhG-CSF of at least 300 μg/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/μl), decreased total blood leukocyte count returned to the normal physiological level and a maximum (7000-16000/μl) 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.
关键词：granulocyte colony-stimulating factor;leukopoietic effect;cyclophoshamide-induced leukopenia;rectal absorption;hollow-type suppository;leukopenic rabbit