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  • Title: Effect of in vivo increase of free fatty acids on human plasma protein binding of furosemide.
    Author: Colombo R, Pinelli A.
    Journal: Pharmacology; 1982; 25(2):73-81. PubMed ID: 7134262.
    Abstract:
    The in vivo effects of increased free fatty acid (FFA) plasma levels on the protein binding of furosemide were investigated in 30 adult-onset diabetics and 22 patients suffering from bacterial infections (gram- negative bacilli and gram-positive cocci). In diabetics, FFA were 2.43 +/- 1.63 mEq/l, and in subjects with bacterial infections 1.82 +/- 0.92 mEq/l. Furthermore, the percent of oleic acid and, to a very lesser extent, palmitoleic acid increased linearly with the increase of the FFA plasma level. The free furosemide fraction was about 1% or less in subjects with a molar ratio of FFA to albumin below 4, but a displacement of the drug from the plasma proteins occurred consistently when this ratio was above 4. At a molar ratio of FFA to albumin as high as 9.34, the free furosemide was 6.7% of the total concentration (8.9 microgram/ml). These results do not quantitatively agree with previous in vitro studies employing single fatty acids and human serum albumin, suggesting that in vivo plasma composition is not adequately reproduced during in vitro experiments on protein-binding displacement of drugs by FFA.
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