腸内におけるサイクロスポリンのファーストパス代謝
J C Kolars1, W M Awni, R M Merion
1Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Lancet (London, England)
|December 14, 1991
まとめ
シクロスポリンは主に肝臓で代謝されます. しかし,この研究では小腸におけるサイクロスポリンの大幅な分解が認められ,その口腔からの吸収が悪いことと薬物相互作用が説明されている.
科学分野:
- 薬理学 薬理学とは
- 胃腸内科 胃腸内科
- 移植医学 移植医学について
背景:
- サイクロスポリン (サイクロスポリンとも呼ばれる) は,免疫抑制薬である.
- 肝臓がサイクロスポリン代謝の唯一の場所であると広く信じられています.
- サイクロスポリン代謝の理解は,治療目的での使用を最適化し,副作用の管理に不可欠です.
研究 の 目的:
- サイクロスポリン代謝における小腸の役割を調査する.
- 肝臓の循環の前にサイクロスポリンが胃腸に分解されるかどうかを判断する.
主な方法:
- 2人の肝臓移植患者の小腸に直接サイクロスポリンを投与.
- アンヘパティックフェーズ (肝臓が摘出される時) のポータル静脈血の採取.
- サイクロスポリン代謝産物の存在に対するポータル静脈血の分析.
主要な成果:
- サイクロスポリン代謝物は,ポータル静脈血液で容易に検出されました.
- ポータル・ブラッドのメタボリットの存在は,肝臓に到達する前に腸内代謝が起こったことを示しています.
結論:
- 小腸はサイクロスポリン代謝の重要な部位である.
- 腸内代謝は,サイクロスポリンの可変な経口生物利用性に寄与する可能性があります.
- この発見は,サイクロスポリンを含む観察された薬物相互作用を説明する可能性がある.
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