In Vivo Pharmacokinetics and Pharmacodynamics of Positional Isomers of Mono-PEGylated Recombinant Human Granulocyte Colony Stimulating Factor in Rats
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- Kang Jung Seok
- Drug Targeting Laboratory, School of Pharmacy, SungKyunKwan University
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- Lee Kang Choon
- Drug Targeting Laboratory, School of Pharmacy, SungKyunKwan University
書誌事項
- タイトル別名
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- <i>In Vivo</i> Pharmacokinetics and Pharmacodynamics of Positional Isomers of Mono-PEGylated Recombinant Human Granulocyte Colony Stimulating Factor in Rats
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In this study, the pharmacokinetic and pharmacodynamic properties of Lys35, MetN-terminal, and Lys17-mono-PEGylated recombinant human granulocyte colony stimulating factor (rhG-CSF) positional isomers were evaluated in rats. The in vitro biological activities of Lys35, MetN-terminal, and Lys17-mono-PEGylated rhG-CSF were determined by examining NFS-60 cell proliferation. Plasma concentrations of rhG-CSF and white blood cell (WBC) counts and absolute neutrophil conunt (ANC) were measured and pharmacokinetic and pharmacodynamic properties were determined after a single subcutaneous administration of the Lys35, MetN-terminal, or Lys17 isomers at 0.1 mg/kg in rats. The in vitro biological activities of Lys35, MetN-terminal, and Lys17-mono-PEGylated rhG-CSF individual positional isomers were 20.1%, 37.4%, and 15.3%, respectively, that of rhG-CSF. However, all three mono-PEGylated rhG-CSF isomers had a greater blood half-life (T1/2) and in vivo efficacy as determined by WBC counts and ANC than rhG-CSF, but no significant difference was observed between the three isomers. In conclusion, Lys35, MetN-terminal, and Lys17-mono-PEGylated rhG-CSF individual positional isomers exhibit an enhanced the in vivo pharmacokinetics and pharmacodynamics. Furthermore, three isomers have comparable in vivo pharmacokinetic and pharmacodynamic properties, but their in vitro biological activities are PEGylation site dependent.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 36 (7), 1146-1151, 2013
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204632544896
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- NII論文ID
- 130003361475
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC3sjmsVKlsw%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 024644672
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- PubMed
- 23811564
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- PubMed
- CiNii Articles
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- 使用不可