HIV感染におけるコトリモクサゾールの副作用

A J van der Ven¹, P P Koopmans, T B Vree

¹Department of Internal Medicine, University Hospital St Radboud Nijmegen, The Netherlands.

Lancet (London, England)

|August 17, 1991

まとめ

コトリモクサゾールの副作用は,グルタチオン欠乏症によるHIV陽性患者においてより一般的です. この欠乏は,反応性代謝物を中和する身体の能力を低下させ,毒性を高めます.

科学分野:

薬理学薬理学とは
免疫学免疫学とは
感染症感染症は感染症です.

背景:

コートリモクサゾールは,ヒト免疫不全ウイルス (HIV) 患者の副作用と頻繁に関連しています.
この感受性の増大の背後にある正確なメカニズムは不明である.
コトリモクサゾールの母化合物の血濃度に関する既存のデータは不確定である.

研究の目的:

HIV陽性個体におけるコトリモクサゾール関連の副作用の増加の根本的な原因を調査する.
これらの有害事象の原因となる特定の代謝産物を特定する.

主な方法:

コトリモクサゾールの代謝と副作用に関する既存の文献のレビュー.
原薬の血濃度に関するデータの分析.
HIV患者におけるグルタチオン欠乏の役割の評価.

主要な成果:

証拠によると,スルファメトキサゾールのヒドロキシラミン誘導体は,有害反応を引き起こす反応性代謝産物である.
HIV陽性の個人は,全身的なグルタチオンの欠乏を示します.
この欠乏は,有毒な代謝物を中和する能力を低下させ,曝露を増加させます.

結論:

HIV患者の全身グルタチオン欠乏症は,反応性スルファメトキサゾール代謝物の解毒を阻害する.
この低下した解毒経路は,この集団におけるコトリモクサゾールに対する副作用の頻度の増加を説明する.
グルタチオンのレベルをターゲットにしたり,解毒経路を強化したりすることで,HIV患者におけるコトリモクサゾールの毒性を軽減することができます.

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