Protein Binding of Quinolonecarboxylic Acids. I. Cinoxacin, Nalidixic Acid and Pipemidic Acid

• 和泉 太郎

  Shionogi Research Laboratories, Shonogi & Co., Ltd.,

• 北川 隆康

  Shionogi Research Laboratories, Shonogi & Co., Ltd.,

抄録

Binding of cinoxain (CINX), nalidixic acid (NA) and pipemidic acid (PPA) to serum proteins was investigated by equilibrium dialysis, ultrafiltration and circular dichroism (CD) spectroscopy. CINX and NA were found to bind mainly to albumin in human serum, the latter interacting with the protein about ten times as strongly as CINX at pH 7.4 and 37℃. PPA showed little or no significant binding to human serum albumin (HSA), α1-acid glycoprotein, and globulins, but showed 20-30% binding to protein in human serum. The CD results were suggestive of some weak interaction of PPA with human apotransferrin. Binding of the three drugs to HSA was found to depend on the lipophilicity of their substituents at the 7-position. The degree of protein binding for human, dog and rat sera at 37℃ was in the order of NA (92-97%)>CINX (68-90%)>PPA (20-30%) at drug concentrations of 10-30μg/ml. CINX showed relatively large species dependence in serum protein binding, which seemed to be due to different affinities of this drug to the respective albumins. CINX was found to bind to rat serum albumin as strongly as NA.

収録刊行物

• Chemical & pharmaceutical bulletin

  Chemical & pharmaceutical bulletin 37 (3), 742-745, 1989-03-25

  公益社団法人日本薬学会

キーワード

• cinoxacin
• nalidixic acid
• pipemidic acid
• albumin
• binding parameter
• substituent effect
• lipophilicity
• pK_a
• serumprotein binding
• species dependence

詳細情報

• CRID: 1571135652461836544
• NII論文ID: 110003627598
• NII書誌ID: AA00602100
• ISSN: 00092363
• 本文言語コード: en
• データソース種別:
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