Effect of mefenamic acid on plasma protein-thyroid hormone interaction, monodeiodination of thyroxine, urinary excretion of tri-iodothyronine and thyrotropin regulation.
A single oral dose of mefenamic acid significantly depressed plasma thyroxine (T4) within 3 h in man. Similarly, mefenamic acid depressed plasma T4 within 3 h in thyroidectomized, T4-maintained rats. Plasma free fractions of T4 and tri-iodothyronine (T3) increased significantly after a single oral administration of mefenamic acid in man. In vitro addition of mefenamic acid to plasma also increased the plasma free fraction of T4. Three times more T3 was excreted into urine after an acute administration of mefenamic acid. In vitro conversion of T4 to T3 by liver homogenate was stimulated when T4 was displaced from plasma binding protein by mefenamic acid. Pituitary content of T3 increased when mefenamic acid displaced T4 and T3 from the binding protein. Simultaneously, thyrotropin (TSH) secretion in response to thyrotropin releasing hormone (TRH) was completely blocked by mefenamic acid. Prolactin release in response to TRH and luteinizing hormone (LH) and follicle stimulating hormone (FSH) release in response to luteinizing hormone releasing hormone (LH-RH) were not affected by mefenamic acid. It is concluded that mefenamic acid displaces T3 and T4 from their plasma binding protein and more T4 and T3 are available to peripheral tissues for excretion, degradation and TSH regulation.
D001798:Blood Proteins / Q000378:metabolism*; D006065:Gonadotropins, Pituitary / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D008528:Mefenamic Acid / Q000494:pharmacology*; D013963:Thyroid Hormones / Q000378:metabolism*; D013965:Thyroidectomy; D013972:Thyrotropin / Q000652:urine*; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism / Q000652:urine*
D001798:Blood Proteins; D006065:Gonadotropins, Pituitary; D013963:Thyroid Hormones; D014284:Triiodothyronine; D008528:Mefenamic Acid; D013972:Thyrotropin; D013974:Thyroxine