Peringatan Keamanan

LD₅₀=20 mg/kg (orally in rat). Hypermetabolic state indistinguishable from thyrotoxicosis of endogenous origin. Symptoms of thyrotoxicosis include weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressure, cardiac arrhythmias, tremors, insomnia, heat intolerance, fever, and menstrual irregularities.

Levothyroxine

DB00451

small molecule approved

Deskripsi

Levothyroxine is a synthetically produced form of thyroxine, a major endogenous hormone secreted by the thyroid gland.^F4633 Also known as L-thyroxine or the brand name product Synthroid, levothyroxine is used primarily to treat hypothyroidism, a condition where the thyroid gland is no longer able to produce sufficient quantities of the thyroid hormones T₄ (tetraiodothyronine or thyroxine) and T₃ (triiodothyronine or DB00279), resulting in diminished down-stream effects of these hormones. Without sufficient quantities of circulating thyroid hormones, symptoms of hypothyroidism begin to develop such as fatigue, increased heart rate, depression^A179620, dry skin and hair, muscle cramps, constipation, weight gain, memory impairment, and poor tolerance to cold temperatures.F4636,A35722

In response to Thyroid Stimulating Hormone (TSH) release by the pituitary gland, a normally functioning thyroid gland will produce and secrete T₄, which is then converted through deiodination (by type I or type II 5?-deiodinases)^A179941 into its active metabolite T₃. While T₄ is the major product secreted by the thyroid gland, T₃ exerts the majority of the physiological effects of the thyroid hormones; T₄ and T₃ have a relative potency of ~1:4 (T4:T3).^F4633 T₄ and T₃ act on nearly every cell of the body, but have a particularly strong effect on the cardiac system.^A179935 As a result, many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status.^A179938

Prior to the development of levothyroxine, DB09100 or desiccated thyroid, used to be the mainstay of treatment for hypothyroidism. However, this is no longer recommended for the majority of patients due to several clinical concerns including limited controlled trials supporting its use. Desiccated thyroid products contain a ratio of T4 to T3 of 4.2:1, which is significantly lower than the 14:1 ratio of secretion by the human thyroid gland. This higher proportion of T3 in desiccated thyroid products can lead to supraphysiologic levels of T3 which may put patients at risk of thyrotoxicosis if thyroid extract therapy is not adjusted according to the serum TSH.A35722, F4636

Struktur Molekul 2D

Berat 776.87

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) T<sub>4</sub> half-life is 6 to 7 days. T<sub>3</sub> half-life is 1 to 2 days.[F4636]

Volume Distribusi -

Klirens (Clearance) -

Absorpsi

Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80% with the majority of the levothyroxine dose absorbed from the jejunum and upper ileum. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans, milk, and dietary fiber. Absorption may also decrease with age. In addition, many drugs affect T4 absorption including bile acide sequestrants, sucralfate, proton pump inhibitors, and minerals such as calcium (including in yogurt and milk products)^A179617, magnesium, iron, and aluminum supplements. To prevent the formation of insoluble chelates, levothyroxine should generally be taken on an empty stomach at least 2 hours before a meal and separated by at least 4 hours from any interacting agents.

Metabolisme

Approximately 70% of secreted T₄ is deiodinated to equal amounts of T₃ and reverse triiodothyronine (rT₃), which is calorigenically inactive. T₄ is slowly eliminated through its major metabolic pathway to T₃ via sequential deiodination, where approximately 80% of circulating T₃ is derived from peripheral T₄. The liver is the major site of degradation for both T₄ and T₃, with T₄ deiodination also occurring at a number of additional sites, including the kidney and other tissues. Elimination of T₄ and T₃ involves hepatic conjugation to glucuronic and sulfuric acids. The hormones undergo enterohepatic circulation as conjugates are hydrolyzed in the intestine and reabsorbed. Conjugated compounds that reach the colon are hydrolyzed and eliminated as free compounds in the feces. Other minor T₄ metabolites have been identified. ^F4636

Rute Eliminasi

Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T₄ is eliminated in the stool. Urinary excretion of T₄ decreases with age.^F4636

Interaksi Makanan

6 Data

1. Avoid calcium supplements/calcium rich foods. Calcium may interfere with the absorption of this drug by forming an insoluble complex. Separate medication administration by at least 4 hours.
2. Avoid grapefruit products. Grapefruit may delay the absorption of this medication.
3. Avoid iron supplements. Iron may interfere with the absorption of this drug by forming an insoluble complex. Separate medication administration by at least 4 hours.
4. Avoid multivalent ions. Examples include iron, magnesium, and calcium. These are often found in antacids, vitamins, and supplements - separate medication administration by at least 4 hours.
5. Do not take with bran and high fiber foods. Dietary fiber, soybean flour, cottonseed meal, and walnuts may reduce the absorption of levothyroxine.
6. Take on an empty stomach. Levothyroxine should be taken on an empty stomach 30-60 minutes prior to the first meal of the day.

Interaksi Obat

760 Data

Afatinib	The serum concentration of Afatinib can be decreased when it is combined with Levothyroxine.
Brentuximab vedotin	The serum concentration of Brentuximab vedotin can be decreased when it is combined with Levothyroxine.
Dabigatran etexilate	The serum concentration of Dabigatran etexilate can be decreased when it is combined with Levothyroxine.
Paliperidone	The serum concentration of Paliperidone can be decreased when it is combined with Levothyroxine.
Sofosbuvir	The serum concentration of Sofosbuvir can be decreased when it is combined with Levothyroxine.
Sucralfate	Sucralfate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminum hydroxide	The serum concentration of Levothyroxine can be decreased when it is combined with Aluminum hydroxide.
Orlistat	The serum concentration of Levothyroxine can be decreased when it is combined with Orlistat.
Raloxifene	Raloxifene can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Sevelamer	The serum concentration of Levothyroxine can be decreased when it is combined with Sevelamer.
Iron sucrose	The serum concentration of Levothyroxine can be decreased when it is combined with Iron sucrose.
Ledipasvir	The serum concentration of Ledipasvir can be decreased when it is combined with Levothyroxine.
Cimetidine	Cimetidine can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Nizatidine	Nizatidine can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ranitidine	Ranitidine can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Famotidine	Famotidine can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Methantheline	Methantheline can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium	Aluminium can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium oxide	Magnesium oxide can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Sodium bicarbonate	Sodium bicarbonate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium carbonate	Calcium carbonate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Metiamide	Metiamide can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Roxatidine acetate	Roxatidine acetate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magaldrate	Magaldrate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium hydroxide	Magnesium hydroxide can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium trisilicate	Magnesium trisilicate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium carbonate	Magnesium carbonate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Lafutidine	Lafutidine can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Lavoltidine	Lavoltidine can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Bismuth subnitrate	Bismuth subnitrate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium silicate	Magnesium silicate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium acetoacetate	Aluminium acetoacetate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Hydrotalcite	Hydrotalcite can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium peroxide	Magnesium peroxide can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Almasilate	Almasilate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium glycinate	Aluminium glycinate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aloglutamol	Aloglutamol can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Niperotidine	Niperotidine can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium silicate	Calcium silicate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium phosphate	Aluminium phosphate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Omeprazole	Omeprazole can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Lansoprazole	Lansoprazole can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Pantoprazole	Pantoprazole can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Esomeprazole	Esomeprazole can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Rabeprazole	Rabeprazole can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Dexlansoprazole	Dexlansoprazole can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Dexrabeprazole	Dexrabeprazole can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Sodium zirconium cyclosilicate	Sodium zirconium cyclosilicate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Vonoprazan	Vonoprazan can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Iron Dextran	Iron Dextran can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Iron	Iron can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Prussian blue	Prussian blue can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferric pyrophosphate	Ferric pyrophosphate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferric ammonium citrate	Ferric ammonium citrate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferumoxsil	Ferumoxsil can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferumoxides	Ferumoxides can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferric sulfate	Ferric sulfate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferrous bisglycinate	Ferrous bisglycinate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Gleptoferron	Gleptoferron can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferric oxide	Ferric oxide can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Perflubutane	Perflubutane can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferrous sulfate anhydrous	Ferrous sulfate anhydrous can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Sodium feredetate	Sodium feredetate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferric hydroxide	Ferric hydroxide can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferric cation	Ferric cation can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferrous gluconate	Ferrous gluconate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferrous succinate	Ferrous succinate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferrous fumarate	Ferrous fumarate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Tetraferric tricitrate decahydrate	Tetraferric tricitrate decahydrate can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferric oxyhydroxide	Ferric oxyhydroxide can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Ferric maltol	Ferric maltol can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Iron polymaltose	Iron polymaltose can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Tolevamer	Tolevamer can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Doxorubicin	The serum concentration of Doxorubicin can be decreased when it is combined with Levothyroxine.
Vincristine	The serum concentration of Vincristine can be decreased when it is combined with Levothyroxine.
Ciprofloxacin	Ciprofloxacin can cause a decrease in the absorption of Levothyroxine resulting in a reduced serum concentration and potentially a decrease in efficacy.
Chlorotrianisene	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Chlorotrianisene.
Tibolone	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Tibolone.
Polyestradiol phosphate	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Polyestradiol phosphate.
Zeranol	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Zeranol.
Equol	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Equol.
Methallenestril	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Methallenestril.
Epimestrol	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Epimestrol.
Moxestrol	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Moxestrol.
Biochanin A	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Biochanin A.
Formononetin	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Formononetin.
Ritanserin	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Ritanserin.
Alaproclate	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Alaproclate.
Sertraline	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Sertraline.
Fluoxetine	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Fluoxetine.
Trazodone	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Trazodone.
Sibutramine	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Sibutramine.
Escitalopram	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Escitalopram.
Fluvoxamine	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Fluvoxamine.
Citalopram	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Citalopram.
Duloxetine	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Duloxetine.
Paroxetine	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Paroxetine.
Nefazodone	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Nefazodone.
Zimelidine	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Zimelidine.
Dapoxetine	The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Dapoxetine.

Target Protein

Integrin alpha-V ITGAV

Integrin beta-3 ITGB3

Thyroid hormone receptor alpha THRA

Thyroid hormone receptor beta THRB

Referensi & Sumber

Synthesis reference: Jivn-Ren Chen, Dimitri C. Papadimitriou, "Stable dosage of levothyroxine sodium and process of production." U.S. Patent US5225204, issued November, 1991.

Artikel (PubMed)

PMID: 11901210
Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H: Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002 Apr;61(4):729-37.
PMID: 20051527
Cheng SY, Leonard JL, Davis PJ: Molecular aspects of thyroid hormone actions. Endocr Rev. 2010 Apr;31(2):139-70. doi: 10.1210/er.2009-0007. Epub 2010 Jan 5.
PMID: 29589994
Chon DA, Reisman T, Weinreb JE, Hershman JM, Leung AM: Concurrent Milk Ingestion Decreases Absorption of Levothyroxine. Thyroid. 2018 Apr;28(4):454-457. doi: 10.1089/thy.2017.0428. Epub 2018 Mar 28.
PMID: 31214119
Tang R, Wang J, Yang L, Ding X, Zhong Y, Pan J, Yang H, Mu L, Chen X, Chen Z: Subclinical Hypothyroidism and Depression: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2019 Jun 4;10:340. doi: 10.3389/fendo.2019.00340. eCollection 2019.
PMID: 27718637
Gottwald-Hostalek U, Uhl W, Wolna P, Kahaly GJ: New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials. Curr Med Res Opin. 2017 Feb;33(2):169-174. doi: 10.1080/03007995.2016.1246434. Epub 2016 Oct 21.
PMID: 24680385
Osmak-Tizon L, Poussier M, Cottin Y, Rochette L: Non-genomic actions of thyroid hormones: Molecular aspects. Arch Cardiovasc Dis. 2014 Apr;107(4):207-11. doi: 10.1016/j.acvd.2014.02.001. Epub 2014 Mar 26.
PMID: 11172193
Klein I, Ojamaa K: Thyroid hormone and the cardiovascular system. N Engl J Med. 2001 Feb 15;344(7):501-9. doi: 10.1056/NEJM200102153440707.
PMID: 6595194
Kaplan MM, Breitbart R: Conversion of thyroxine to triiodothyronine in the anterior pituitary gland and the influence of this process on thyroid status. Horm Metab Res Suppl. 1984;14:79-85.

Menampilkan 8 dari 12 artikel.

Link

Attachment

Contoh Produk & Brand

Produk: 1434 • International brands: 6

Produk

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Adthyza thyroid

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Adthyza Thyroid

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Adthyza Thyroid

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Adthyza Thyroid

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Menampilkan 8 dari 1434 produk.

International Brands

Eutirox — Merck
Letrox — Berlin-Chemie
Levaxin — Nycomed
Levothyrox — Merck
Oroxine — GlaxoSmithKline
Thyrax — Merck

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.