levothyroxine

Levothyroxine is a commonly prescribed drug. It is used as replacement therapy for patients with hypothyroidism or as interventional therapy to suppress the serum thyroid-stimulating hormone (TSH) concentration in patients with nodular thyroid disease or Thyroid Neoplasms [Articles:8357116, 9490600]. Levothyroxine is synthetically produced but is identical to T4, which is the major hormone secreted by the thyroid.

Pharmacokinetics:

Levothyroxine is readily absorbed following ingestion. Similar to the endogenous thyroid hormone thyroxine, or T4, it is converted to its active metabolite T3 in liver and peripheral tissues by the action of thyroxin deiodinases (DIO1, DIO2, DIO3) [Articles:18279024, 16214936]. Some of the T4 and T3 is conjugated with glucuronide (through the action of UGT1A1, UGT1A9 , UGT2B@ ) and sulfate (possibly via SULT1A1) in the liver [Articles:16131336, 10946897] and then excreted in bile and partially hydrolyzed in the intestine to be reabsorbed [Articles:7477223, 2070777]. An in vitro study showed that levothyroxine upregulates expression of P-Glycoprotein (P-gp, ABCB1) but not CYP3A4 in a PXR-independent mechanism, suggesting possible drug-drug interactions mediated by P-gp [Article:15258100].

Pharmacodynamics:

The action of T3 is initiated by the thyroid hormone receptors (THRA, THRB), which can form dimers with retinoid X receptors to regulate transcription of target genes. T4 and T3 can inhibit the secretion of thyrotropin (TSH, TSHB, CGA) directly or indirectly through inhibiting the secretion of thyrotropin-releasing hormone (TRH) [Articles:7477223, 12432094, 12419821, 11278601].