Pharmacodynamics and Pharmacokinetics of Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) after Administration of a Rectal Dosage Vehicle

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概要

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• The pharmacodynamic activities (leukopoietic effect) and pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administered rectally in various doses as hollow-type suppositories were investigated in rabbits. Three kinds of rhG-CSF hollow-type suppositories were employed : suppository I containing rhG-CSF (100-1000 μg/kg) in 10 mM acetate buffer solution (ABS) at pH 4.0,suppository II containing rhG-CSF in ABS with α-cyclodextrin (α-CyD) as an absorption-enhancing agent, and suppository III containing lyophilized rhG-CSF powder. We found that the total count of leukocytes in peripheral blood (total blood leukocyte count) and serum granulocyte colony-stimulating factor (G-CSF) concentration showed a dose-dependent increase. Consequently, the area under the increased total blood leukocyte count-time curve (AUL), an index of pharmacodynamic activity, and the area under the serum G-CSF concentration-time curve (AUC), a pharmacokinetic parameter, increased with an increase in the rhG-CSF dose administered rectally. Good correlation was found between AUL and AUC;thus, it is concluded that an increase in AUC leads to an increase in the effect of rhG-CSF in inducing leukopoiesis in rabbits following rectal administration. We report for the first time the rectal absorption of rhG-CSF using a new rectal dosage vehicle (rhG-CSF hollow-type suppository) and its leukopoietic effect. The rhG-CSF hollow-type suppository is found to be a promising drug delivery system.

• 公益社団法人日本薬学会の論文
• 1996-08-15

著者

• Matsumoto M

  Osaka Medical Center For Cancer And Cardiovascular Diseases Osaka

• Matsumoto Misako

  Department Of Immunology Osaka Medical Center For Cancer And Cardiovascular Diseases

• Watanabe Yoshiteru

  Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University

• Nomura H

  Pharmaceutical Development Laboratory Kirin Brewery Co. Ltd.

• Nomura Hideaki

  Pharmaceutical Development Laboratories Kirin Brewery Company Ltd

• Matsumoto Mitsuo

  Department of Pharmaceutics, Showa Pharmaceutical University

• Matsumoto Mitsuharu

  Takeda Chemical Industries Ltd. Pharmaceutical Research Division

• Watanabe Yoshiteru

  Department Of Pharmaceutics And Biopharmaceutics Showa Pharmaceutical University

• Watanabe Y

  Showa Pharmaceutical Univ.

• Kikuchi R

  Faculty Of Pharmaceutical Sciences Kanazawa University

• 菊地 利恵

  Department Of Pharmaceutics Showa College Of Pharmaceutical Sciences

• Matsumoto Mitsuo

  Department Of Pharmaceutics Showa Pharmaceutical University

• Watanabe Yoshiteru

  Showa Pharmaceutical Univ.

• MIZUFUNE Yuko

  Department of Pharmaceutics, Showa College of Pharmaceutical Sciences

• KIRIYAMA Miyuki

  Department of Pharmaceutics, Showa College of Pharmaceutical Sciences

• KIKUCHI Rie

  Department of Pharmaceutics, Showa College of Pharmaceutical Sciences

• ITO Ritsuko

  Department of Pharmaceutics, Showa College of Pharmaceutical Sciences

• MIYAZAKI Masanao

  Pharmaceutical Development Laboratory, Kirin Brewery Co., Ltd.,

• Matsumoto Mitsuhiro

  First Department Of Internal Medicine Kumamoto University School Of Medicine

• Matsumoto Mitsuo

  Department Of Pharmaceutics And Biopharmaceutics Showa Pharmaceutical University

• Ito Ritsuko

  Department Of Pharmaceutics Showa College Of Pharmaceutical Sciences

• Ito Ritsuko

  Department Of Neuropsychiatry Nippon Medical School

• Mizufune Yuko

  Department Of Pharmaceutics Showa College Of Pharmaceutical Sciences

• Kuriyama M

  Department Of Pharmaceutics Showa College Of Pharmaceutical Sciences

• Miyazaki Masanao

  Pharmaceutical Development Laboratory Kirin Brewery Co. Ltd.

• Matsumoto Mitsuo

  Department Of Ophthalmology Hirosaki University School Of Medicine

• Matsumoto Mitsuo

  Department of Hydrocarbon Chemistry, Faculty of Engineering, Kyoto University

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