Xenobiotics of Levothyroxine
Levothyroxine (Synthroid) is a synthetic T4 hormone that is used to treat hypothyroidism, goiters, subacute or chronic lymphocytic thyroiditis, and for thyroid cancer patients who have underwent thyroidectomy. Levothyroxine is absorbed in the duodenum, jejunum, and ileum and is meant to be taken without food. The absorption is also determined by the pH of the gastric acid within the stomach. The main metabolic route of T4 involves the removal of an outer ring iodine by deiodinase enzymes; in which it then becomes T3. In some instances, there’s deionization of the inner molecule and produces an inactive reverse T3 known as rT3 (Colucci et al., 2013). About fifty percent of T4 is metabolized to rT3. Both rT3 and T3 is further metabolized to T2 and T1 and rT2 and rT1. The half-life for T4 is about 7.5 days in hypothyroid patients (Colucci et al., 2013). About 80% of T4 and T3 bind predominately to thyroxin-binding globulin (TBG) and the rest to thyroxine-binding pre-albumin and albumin (Colucci et al., 2013). Active transport of thyroxine into the cells is through organic anion transporting peptides (OATP), monocarboxylate transporter, and sodium-taurocholate co-transporting polypeptides (Colucci et al., 2013). The kidneys play an important role in metabolizing T4 and T3. It is common for those with end-stage renal impairment to also have hypothyroidism. The liver is where the majority of the deiodination from T4 to T3 occurs and then are coupled with glucuronic and sulphuric acids which are excreted in the bile (Colucci et al., 2013).
This drug is offered in liquid, tablet, and soft gel capsules. The liquid form is absorbed faster than tablets however, is less dependable, depending on the gastric pH, but lowers TSH more effectively than other forms (Wiesner et al., 2021). It also maintains stability when taken with beverages such as milk, tea, coffee, coffee with milk, and orange juice (Wiesner et al., 2021). Softgels can be effectively absorbed when the gastric pH is higher compared to tablets and also be taken with breakfast without a significant difference in TSH levels. (Wiesner et al., 2021).
The proper usage of the tablet levothyroxine is to take it at least 3 hours of having food and one hour before eating. Studies have shown an absorption decrease from fifteen to forty percent (Wiesner et al., 2021). Food contraindications include Activated charcoal because it absorbs various drugs reducing their absorption or half-life (Therapeutic Research Center, 2024). Coffee has been shown to decrease the absorption of this drug and is suggested to have no coffee consumption for at least an hour after taking the drug (Wiesner et al., 2021).
Drug contraindications include those who are taking omeprazole, and lansoprazole require higher levels of levothyroxine. Combined use with Tiratricol may have additive effects (Therapeutic Research Center, 2024). Drugs that decrease TSH secretion such as dopamine, glucocorticoids, octreotide and rexinoids impact the bioavailability and absorption of levothyroxine (Colucci et al., 2013). Aluminum hydroxide, dietary fiber, calcium carbonate, calcium citrate, calcium acetate, ferrous sulphate, choestyramine and colsevelam bind to levothyroxine and form complexes that prevent it from being absorbed therefore decreases its effectiveness (Colucci et al., 2013). Sucralphate binds to intra-luminal transport which interferes with levothyroxine ability to be absorbed. Beta blockers such as acebutolol, oxprenolol and timolol the extracellular distribution of T3, causing an increase in rT3 which makes it more readily to be removed from the body (Colucci et al., 2013).
As a pharmacy technician, I have only seen the use of tablet form Levothyroxine (Synthroid), so I think it’s important that patients understand the importance of compliance when taking this form of the drug. Without being in compliance, the person may need to take a higher dosage.
Resources:
Wiesner, A., Gajewska, D., & Paśko, P. (2021). Levothyroxine interactions with food and dietary supplements–a systematic review. Pharmaceuticals, 14(3), 206. https://doi.org/10.3390/ph14030206
Colucci, P., Yue, C. S., Ducharme, M., & Benvenga, S. (2013). A review of the pharmacokinetics of levothyroxine for the treatment of hypothyroidism. European Endocrinology, 9(1), 40–47. https://doi.org/10.17925/ee.2013.09.01.40
Therapeutic Reserach Center. (2024). NATMED Pro. NatMed Pro. https://naturalmedicines.therapeuticresearch.com/#
