非ステロイド性抗炎症薬からみたキノロン系薬との薬物相互作用 : Gatifloxacinとnorfloxacinの比較検討  [in Japanese] Convulsant activity of norfloxacin and gatifloxacin and interaction with antiinflammatory drugs  [in Japanese]

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Abstract

われわれは, 非ステロイド薬 (NSAIDs) とキノロン薬の薬物相互作用の強さを, mouse脳室内投与によるnorfloxacin (NFLX) およびgatinoxacin (GFLX) の痙攣誘発作用を指標として検討した。NFLXおよびGFLXの脳室内投与によりmouseに投与量依存的に痙攣が誘発され, その痙攣誘発作用はNFLX<GFLXであった。NFLXの痙攣誘発作用は, biphenylacetic acid (BPA), flurbiprofenの同時投与により増強された。Indomethacin, ketoprofenでは中等度の, loxoprofen,(-)-naproxenでは軽度の痙攣誘発作用増強が認められたが, ibuprofen, sodium diclofenac, mefenamic acid, tenoxicam,(+)-naproxen, aspirinおよびacetaminophenでは変化が見られなかった。一方, GFLXの痙攣誘発作用は, BPAで軽度増強されたものの, 他のNSAIDsでは変化を認めなかった。以上の成績より, NSAIDsによりキノロン薬との薬物相互作用の強さに違いがあり, さらに, キノロン薬との組み合わせによっても差のあることが明らかとなった。

Quinolones have potent convulsant activity and that the activity is enhanced by the concurrent administration of anti-inflammatory drugs. We studied the effect of antiinflammatory drugs on the convulsant activity of norfloxacin (NFLX) and gatifloxacin (GFLX) to classify antiinflammatory drugs based on drug interaction with quinolones. Intraventricular injection of NFLX induced convulsions dosedependently in mice. The convulsant activity of NFLX was markedly enhanced by coadministration with biphenylacetic acid and flurbiprofen. Indomethacin and ketoprofen had intermediate enhancing activity, and loxiprofen and (-)-naproxen had weak activity. Mefenamic acid, sodium diclofenac, ibuprofen, tenoxicam, naproxen, aspirin and acetaminophen did not affect the activity. Intraventricular injection of GFLX induced convulsions dose-dependently in mice with weaker convulsant activity than NFLX. The convulsant activity of GFLX was weakly enhanced by coadministration of biphenylacetic acid. Other antiinflammatory drugs examined in this study did not affect the activity of GFLX. These results suggest that individual antiinflammatory drugs have different effects on drug interaction with quinolones.

Journal

  • Japanese Journal of Chemotherapy

    Japanese Journal of Chemotherapy 50(7), 460-463, 2002-07-25

    Japanese Society of Chemotherapy

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