Protein binding of quinolonecarboxylic acids. I. Cinoxacin, nalidixic acid and pipemidic acid.
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 degrees C. PPA showed little or no significant binding to human serum albumin (HSA), alpha 1-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 degrees C was in the order of NA (92-97%) greater than CINX (68-90%) greater than PPA (20-30%) at drug concentrations of 10-30 micrograms/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.
Izumi
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Kitagawa
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D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002937:Cinoxacin / Q000097:blood*; D003956:Dialysis; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D009268:Nalidixic Acid / Q000097:blood*; D009539:Nicotinic Acids / Q000097:blood*; D010876:Pipemidic Acid / Q000097:blood*; D011485:Protein Binding; D011724:Pyridazines / Q000097:blood*; D051381:Rats; D013045:Species Specificity
D001798:Blood Proteins; D009539:Nicotinic Acids; D011724:Pyridazines; D009268:Nalidixic Acid; D002937:Cinoxacin; D010876:Pipemidic Acid