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  • Title: A naturally occurring furan fatty acid enhances drug inhibition of thyroxine binding in serum.
    Author: Lim CF, Stockigt JR, Curtis AJ, Wynne KN, Barlow JW, Topliss DJ.
    Journal: Metabolism; 1993 Nov; 42(11):1468-74. PubMed ID: 8231843.
    Abstract:
    We studied the thyroxine (T4)-displacing effects of a naturally occurring, highly albumin-bound furanoid acid that accumulates in serum in renal failure to concentrations in excess of 0.2 mmol/L. This substance, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), has been shown to displace acidic drugs from albumin binding. The effects of CMPF on ligand binding were assessed in the following systems: (1) T4 binding to T4-binding globulin (TBG) and transthyretin (TTR), (2) T4 binding in undiluted serum, (3) T4-displacing potency of fenclofenac, furosemide, diflunisal, and aspirin in undiluted serum, (4) serum binding of [14C]-drug preparations, and (5) serum binding of [14C]-oleic acid. CMPF had a minor direct effect on T4 binding to TBG comparable in relative affinity to that of aspirin, ie, almost 7 orders of magnitude less than T4 itself. CMPF alone at a concentration of 0.3 mmol/L, which produced only a 10% to 14% increase in free T4 augmented the T4-displacing effects of high therapeutic concentrations of the various drugs in undiluted serum as follows: furosemide by 180%, fenclofenac by 160%, diflunisal by 130%, and aspirin by 40%. In the presence of fenclofenac, increments of CMPF from 0.075 to 0.3 mmol/L progressively augmented the T4-displacing effect of this drug, associated with a progressive increase in its calculated free concentration. CMPF also inhibited the binding of [14C]-oleic acid, suggesting that in some situations CMPF could also indirectly influence thyroid hormone binding by increasing the unbound concentration of nonesterified fatty acids (NEFA), as previously described.(ABSTRACT TRUNCATED AT 250 WORDS)
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