Pharmacokinetic/Pharmacodynamic Analysis of Neutrophil Proliferation Induced by Recombinant Granulocyte Colony-Stimulating Factor (rhG-CSF) : Comparison between Intravenous and Subcutaneous Administration
スポンサーリンク
概要
- 論文の詳細を見る
Pharmacological effect after intravenous (i.v.) or subcutaneous (s.c.) administration of human recombinant granulocyte colony stimulating factor (rhG-CSF) was evaluated by using a physiologically based pharmacokinetic/pharmacodynamic model. The increase of neutrophil counts in blood after s.c. administration of rhG-CSF (0.5-1.0 μg/kg) was larger than that after i.v. administration of the same dose, while area under the curves of plasma concentration of rhG-CSF after s.c. administration was smaller than that after i.v. administration (Azuma et al., J. Clin. Therap. Med., 5,1579-1603,1989). Based on the pharmacokinetic/pharmacodynamic model considering metabolic turnover of neutrophil in vitro, time course of absolute neutrophil counts in blood after either type of rhG-CSF administration to normal healthy volunteers was analyzed. The nonlinear relationship between the concentration of rhG-CSF and in vivo activity for proliferation of neutrophil could be explained by the drug-receptor-effector ternary complex model. These in vivo and in vitro models made it possible to understand the above-mentioned discrepancy of pharmacokinetic/pharmacodynamic behavior between i.v. and s.c. administration of rhG-CSF. Simulation of the neutrophil count-time profiles after repeated i.v. and s.c. dosing of rhG-CSF according to these models showed good aggreement with the observed data. In order to obtain the rational dosage regimen of rhG-CSF from pharmacological and economical points of view, a slow constant infusion method may be more useful than rapid infusion.
- 公益社団法人日本薬学会の論文
- 1997-06-15
著者
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SAWADA Yasufumi
Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo
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Sawada Y
Department Of Pharmaceutics Graduate School Of Pharmacertical Sciences Kyushu University
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Sawada Yasufumi
Faculty Of Pharmaceutical Sciences Tokushima Bunri University:faculty Of Pharmaceutical Sciences Uni
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IGA Tatsuji
International University of Health and Welfare
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Yamamoto Koujirou
Department Of Pharmacy The University Of Tokyo Hospital Faculty Of Medicine The University Of Tokyo
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Yamamoto Koujirou
Department Of Pharmacy The Gunma University Hospital Gunma University School Of Medicine:department
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Yamamoto Koujirou
Department Of Clinical Pharmacology Gunma University School Of Medicine
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Yamamoto Koujirou
Department Of Clinical Pharmacology Gunma University Graduate School Of Medicine
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Iga T
Department Of Pharmacy University Of Tokyo Hospital
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Iga Tatsuji
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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Iga T
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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SUGIURA Munetoshi
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
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Sugiura Munetoshi
Department Of Pharmacy University Of Tokyo Hospital Faculty Of Medicine University Of Tokyo
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Yamano Katsuhiro
Biopharmaceutical And Pharmacokinetic Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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