結核性髄膜炎における最適のモキシフロクサシン投与に向けて: 翻訳的生理学的にベースの薬理学動態モデリングアプローチ
Ming Sun1, Katie Lynch2, Theis Mariager3
1Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, the Netherlands; ESCMID Study Group for Infectious Diseases of the Brain (ESGIB), Basel, Switzerland.
まとめ
結核性髄膜炎 (TBM) では,リファンピシンと併用しても,より高いモキシフロクサシン用量が必要になる可能性があります. 800 mgを超える用量は,この重度の中枢神経系感染症の効果的な治療を確保するために,臨床試験における安全性評価を必要とします.
科学分野:
- ファルマコキネティクスとファルマコダイナミクス
- 感染症 感染症は感染症です.
- 神経科学は神経科学である.
背景:
- 結核性髄膜炎 (TBM) は,死亡率が高い重症の中枢神経系感染症である.
- モキシフロキサシンは抗菌活動と中枢神経系への浸透性を有していますが,TBMにおける最適な投与量は不明です,特にリファンピシンとの併用は不明です.
- リファンピシンはモキシフロクサシン暴露を著しく減少させます.
研究 の 目的:
- TBMの最適なモキシフロクサシン用量を決定する.
- 地域の中枢神経系 (CNS) 製薬動態 (PK) とリファンピシンの併用を考慮するために.
- 種間トランスレーション性生理学ベースの薬理動力学 (PBPK) モデルを使用する.
主な方法:
- 豚の血と中枢神経系の微透析データを用いてPBPKモデルを開発しました.
- モデルをアロメトリックスケーリングと文献データを用いて人間に翻訳しました.
- ヒトのPKデータでモデルを検証し,リファンピシンと/なしの様々なモキシフロクサシン用量 (400-1000 mg) をシミュレートしました.
主要な成果:
- PBPKモデルは,豚およびヒトの中枢神経系におけるモキシフロクサシン濃度を正確に記述した.
- 地域的なPKの差異が観察され,最高濃度は脳下関節領域で,最低濃度は脳細胞外流体であった.
- リファンピシンは中枢神経系への曝露を26%減少させ,特にリファンピシンでは,ターゲットレベルに到達するために,より高いモキシフロキサシン用量 (1000 mgまで) が必要であった.
結論:
- PK目標達成を達成するために,TBMにはより高いモキシフロクサシン用量が必要である可能性が高い.
- リファンピシンを併用しても,投与量の調整が必要になる場合があります.
- 800 mgを超えるモキシフロキサシン療法の安全性は,厳格な臨床調査を必要とします.
キーワード:
中枢神経系 (CNS) の薬理学投与量最適化についてモキシフロキサシン (moxifloxacin) とは,モキシフロキサシン (moxifloxacin) とは,モキシフロキサシン (moxifloxacin) とは,モキシフロキサシン (moxifloxacin) とは,モキシフロキサシン (moxifloxacin) とは,モキシフロキサシン (moxifloxacin) とは,モキシフロキサシン (moxifloxacin) とは生理学ベースの薬物動力学 (PBPK) モデリングリファンピシン 薬物相互作用翻訳薬動力学/薬物動力学 (PK/PD)結核性髄膜炎 (TBM) とは
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