Furosemide, fenclofenac, diclofenac, mefenamic acid and meclofenamic acid inhibit specific T3 binding in isolated rat hepatic nuclei

Abstract

Previous studies with Phenytoin (DPH) show that this inhibitor of thyroid hormone binding to plasma proteins also interacts with specific nuclear T3 binding sites. In order to further define the nuclear effects of drugs that inhibit plasma protein binding of thyroid hormones, we assessed furosemide and a number of non-steroidal antiinflammatory drugs using isolated rat liver nuclei. The effects were compared with those of DPH, ipodate and amiodarone. The T3 binding site in isolated nuclei (Ka 1.2×109M−1) showed relative affinity triac ≈ T3>T4. Drugs were studied over the concentration range 10−3-10−7M, approximating the known therapeutic total plasma concentrations, in competition with 125|-..