Interaction of furosemide with serum thyroxine-binding sites: in vivo and in vitro studies and comparison with other inhibitors.
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Stockigt JR, Lim CF, Barlow JW, Wynne KN, Mohr VS, Topliss DJ, Hamblin PS, Sabto J
Interaction of furosemide with serum thyroxine-binding sites: in vivo and in vitro studies and comparison with other inhibitors.
J Clin Endocrinol Metab. 1985 May;60(5):1025-31. doi: 10.1210/jcem-60-5-1025.
- PubMed ID
- 2579968 [ View in PubMed]
- Abstract
The diuretic furosemide inhibits serum protein binding of T4 in equilibrium dialysis, dextran-charcoal, and competitive ligand binding separation systems and displaces [125I]T4 from isolated preparations of T4-binding globulin (TBG), prealbumin, and albumin. Equilibrium dialysis studies of undiluted normal serum showed that about 10 micrograms/ml furosemide increased the free T4 and free T3 fractions. Displacement occurred at lower drug concentrations in sera with subnormal albumin and TBG levels. Binding of [14C]furosemide to TBG was inhibited by unlabeled T4, suggesting that furosemide and T4 share a common binding site. A single oral dose of 500 mg furosemide given to five patients maintained on peritoneal dialysis increased the percentage of charcoal uptake of [125I]T4 (using serum diluted 1:10) from 4.1 +/- 1.0 (+/- SE) to 10.8 +/- 4.3 (P less than 0.01) after 2 h, while decreasing total T3 from 75 +/- 5 to 56 +/- 13 ng/dl (P less than 0.01) and total T4 from 6.7 +/- 0.9 to 4.8 +/- 0.8 micrograms/dl (P less than 0.01) after 5 h. Various ligands inhibited [125I]T4 binding to serum proteins in the following relative molar relationship: T4, 1; furosemide, 1.5 X 10(3); fenclofenac, 2 X 10(4); mefenamic acid. 2.5 X 10(4); diphenylhydantoin, 4 X 10[4); ethacrynic acid, 10(5); heparin 5 X 10(5); 2-hydroxybenzoylglycine, 10(6); and sodium salicylate, 1.5 X 10(6). These studies demonstrate that furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower total T4 and T3 levels. The drug is much more potent on a molar basis than other drug inhibitors of T4 binding, but at normal therapeutic concentrations, furosemide is unlikely to decrease serum T4 or T3. However, high doses, diminished renal clearance, hypoalbuminemia, and low TBG accentuate its T4- and T3-lowering effect. Hence, furosemide should be considered a possible cause of low thyroid hormone levels in patients with critical illness. The significance of this drug in reports of impaired hormone and drug binding in renal failure requires further assessment.
DrugBank Data that Cites this Article
- Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Furosemide Thyroxine-binding globulin Protein Humans NoBinderDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareLevothyroxineFurosemide The protein binding of Levothyroxine can be decreased when combined with Furosemide. LiothyronineFurosemide The protein binding of Liothyronine can be decreased when combined with Furosemide. LiotrixFurosemide The protein binding of Liotrix can be decreased when combined with Furosemide. Thyroid, porcineFurosemide The protein binding of Thyroid, porcine can be decreased when combined with Furosemide.