Influence of Endogenous Substances on Site-II to Site-I Displacement of Diclofenac Bound to Albumin in the Aqueous Humor of Patients with Cataract

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  • Ishii Saya
    Department of Pharmacy, University of Miyazaki Hospital, University of Miyazaki Ozaki Eye Hospital School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
  • Ogata Kenji
    School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
  • Takamura Norito
    School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
  • Tokunaga Jin
    School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
  • Ikeda Ryuji
    Department of Pharmacy, University of Miyazaki Hospital, University of Miyazaki
  • Ozaki Mineo
    Ozaki Eye Hospital

書誌事項

公開日
2024-01-20
資源種別
journal article
DOI
  • 10.1248/bpb.b23-00301
公開者
公益社団法人 日本薬学会

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説明

<p>Diclofenac instillation is useful in preventing intraoperative miosis and macular edema caused by postoperative inflammation in cataract surgery; however, optimum efficacy is not attained when the instilled diclofenac strongly binds to albumin in patients’ aqueous humor. Therefore, a method that inhibits diclofenac binding and increases the concentration of its free fraction is needed. We conducted a basic study regarding the effects of inhibitors on the binding of instilled diclofenac to albumin and endogenous substances in aqueous humor. Aqueous humor samples from 16 patients were pooled together for analysis. The free fraction of diclofenac was measured using ultrafiltration methods in various experiments with pooled and mimic aqueous humor. Free fraction of diclofenac, a site II drug, in pooled aqueous humor was 0.363 ± 0.013. The binding of diclofenac in the presence of phenylbutazone (PB), a site I inhibitor, was significantly inhibited (free fraction = 0.496 ± 0.013); however, no significant inhibition by ibuprofen, a site II inhibitor, (free fraction = 0.379 ± 0.004), was observed. The unexpected result was due to free fatty acids (FFAs; palmitic acid (PA)) and L-tryptophan (Trp). The inhibition of diclofenac binding by PB in the mimic aqueous humor containing these endogenous substances revealed significant binding inhibition in the presence of PA and Trp. Diclofenac is strongly rebound from site II to site I in the presence of FFAs and Trp in the aqueous humor because FFAs and Trp induce a conformational change in albumin. Therefore, PB significantly inhibits the binding of diclofenac to albumin.</p>

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