Endogenous Metabolite; synthetic form of the thyroid hormone thyroxine (T4)

左旋甲状腺素治疗在体外动物模型中产生异常的子宫收缩模式[2]
甲状腺功能筛查证实，在无碘饮食下，所有大鼠都处于甲状腺功能减退状态，随后给予T4以平衡甲状腺功能减退。结果表明，甲状腺功能减退显著缩短了收缩持续时间（-17%），增加了收缩频率（+26%），而高剂量的T4增加了持续时间（+200%），降低了频率（-51%）。因此，这些结果模拟了之前在T4治疗的甲状腺功能减退孕妇的子宫组织中观察到的异常收缩模式。 结论：我们的数据表明，T4治疗会引起子宫肌层反应性的变化。因此，结合我们之前对人类子宫肌层条带的观察，应改进甲状腺功能减退症的治疗，以降低这组患者的剖腹产率[2]。

肾上腺素（皮质原）通过脱碘酶 (DIO) 转化为活跃的肾上腺皮质，而 TSH（催化肾上腺素）的水平与这种反应相关。肾上腺皮质被 DIO1 和 DIO2 激活，并被 DIO3 停用。在垂体TSH的负反馈调节中，DIO1和DIO2的作用起决定性作用[1]。甲状腺素 (T3) 和 L-甲状腺素 (T4) 的离子通道、泵和调节性收缩的调节是成熟的。此外，已证明雄激素影响充电兴奋、钙补充、收缩死亡率以及L-甲状腺素和三碘甲状腺原氨酸的药物控制和摄食调节。与喂食常规饮食的对照组相比，喂食无碘饮食 12 周的队列中三碘甲状腺原氨酸和 L-甲状腺素的水平显着降低（p<0.001）。在接受低剂量 L-甲状腺素治疗的组中，L-甲状腺素水平有所上升 (p=0.02)，尽管三碘甲状腺原氨酸水平 (p=0.19) 与头痛严重程度几乎保持一致。与未接受治疗的甲状腺功能减退组相比，用高剂量 L-甲状腺素治疗后，观察到三碘甲状腺原氨酸和 L-甲状腺素的循环浓度增加（分别为 p<0.001 和 p=0.004）。与对照值相比，甲状腺激素水平显着上升（p=0.03）。

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甲状腺激素在人体的生长和分化、能量代谢调节和生理功能中起着至关重要的作用。甲状腺功能减退症是一种常见的内分泌疾病，通常是由于血清甲状腺素（fT4）和三碘甲状腺原氨酸（fT3）的正常循环浓度降低引起的。甲状腺功能减退症治疗的主要选择是口服左旋甲状腺素（L-T4），一种合成的T4激素，约为100-125μg/天。通常，剂量调整是通过试错法进行的。然而，有几个因素可能会影响L-T4治疗的生物利用度。遗传背景可能是甲状腺功能减退患者的重要因素，年龄、性别、合并用药和患者依从性也是如此。组织中甲状腺激素的浓度受脱碘酶和甲状腺激素转运蛋白的调节。本研究旨在评估土耳其人群中甲状腺激素代谢和L-T4生物利用度中有效的蛋白质和酶（DIO1、DIO2、TSHR、THR和UGT）的遗传差异的影响。根据我们的研究结果，DIO2中的rs225014和rs225015变体与TSH水平有关，DIO2催化甲状腺素（前激素）转化为活性甲状腺激素。rs225014 TT和rs225015 GG基因型患者应给予较低剂量，以提供更有效、更低毒性的适当治疗。[1]

生化技术[2]
根据制造商的方案，使用标准大鼠甲状腺素（T4）和T3 ELISA试剂盒进行ELISA测定。如前所述，进行了蛋白质印迹分析。

Female non-pregnant Sprague-Dawley rats (N = 22) were used and divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low T4 doses (20 μg/kg/day) and 4) with high T4 doses (100 μg/kg/day). Hypothyroidism was induced by an iodine-deficient diet. Isometric tension measurements were performed in vitro on myometrium tissues in isolated organ baths. Contractile activity parameters were quantified (amplitude, duration, frequency and area under the curve) using pharmacological tools to assess their effect.[2]

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Sprague–Dawley female rats (N = 22) were used. Non-pregnant rats were divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low doses of Levothyroxine (T4) (20 μg/kg/day) and 4) with high doses of T4 (100 μg/kg/day). Control rats (group 1) were fed with standard diet (TD.120461, Harlan laboratories, Madison, WI) while the intervention rats were fed with iodine-free diet for 12 weeks to induce hypothyroidism (groups 2–4) which was continued for four more weeks to allow screening of hypothyroid status and T4-treatment. Food and water (iodine-free diet) were available ad libitum. The hypothyroid group treated with low (group 3) or high doses of T4 (group 4) were injected intraperitoneally every 24 h with respectively 20 μg/kg/day and 100 μg/kg/day as previously described by Medeiros. Blood samples were collected for thyroid function screening at week 12 and 16 following the initiation of either the control or iodine-free diet. Hysterectomy was performed under general anesthesia (isoflurane 2%) at the end of the treatment and the two uterine horns were placed in physiological Krebs' solution until isometric tension measurements within no more than 1 h.[2]

Absorption, Distribution and Excretion
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), 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.
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.
Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins. Thyroid hormones do not readily cross the placental barrier.
Levothyroxine Sodium for Injection is administered via the intravenous route. Following administration, the synthetic levothyroxine cannot be distinguished from the natural hormone that is secreted endogenously.
Absorption of orally administered T4 from the gastrointestinal (GI) tract ranges from 40% to 80%. The majority of the levothyroxine dose is absorbed from the jejunum and upper ileum. The relative bioavailability of Synthroid tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 93%. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybean infant formula. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption.
Levothyroxine is variably absorbed from the GI tract (range: 40-80%). In animals, levothyroxine is absorbed in the proximal and middle jejunum; the drug is not absorbed from the stomach or distal colon and little, if any, absorption occurs in the duodenum. Studies in humans indicate that levothyroxine is absorbed from the jejunum and ileum and some absorption also occurs in the duodenum. The degree of absorption of levothyroxine from the GI tract depends on the product formulation and type of intestinal contents, including plasma protein and soluble dietary factors that may bind thyroid hormone and make it unavailable for diffusion. In addition, concurrent oral administration of infant soybean formula, soybean flour, cotton seed meal, walnuts, foods containing large amounts of fiber, ferrous sulfate, antacids, sucralfate, calcium carbonate, cation-exchange resins (e.g., sodium polystyrene sulfonate), simethicone, or bile acid sequestrants may decrease absorption of levothyroxine. The extent of levothyroxine absorption is increased in the fasting state and decreased in malabsorption states (e.g., sprue); absorption also may decrease with age.
For more Absorption, Distribution and Excretion (Complete) data for LEVOTHYROXINE (7 total), please visit the HSDB record page.

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Metabolism / Metabolites
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.
Yields l-tyrosine in rabbit, in rat /From table/
Yields 3,3',5-triiodo-L-thyronine in man, rat, dog, rabbit. /From table/
Yields l-thyroxine-4'-beta-d-glucuronide in dog, in man, in rat. Yields l-thyroxine-4'-sulfate in dog. /From table/
Yields 3,3',5,5'-tetraiodothyropyruvic acid in rat. Yields l-thyronine in rat. /From table/
Yields 3,3'-diiodo-l-thyronine in dog. Yields 3,3',5,5'-tetraiodothyroacetic acid in man, in rat. /From table/

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Biological Half-Life
T₄ half-life is 6 to 7 days. T₃ half-life is 1 to 2 days.
In dogs orally administered levothyroxine has relatively ... short elimination half life when compared to humans. ... The serum half life is approximately 12-16 hours.
The usual plasma half-lives of thyroxine and triiodothyronine are 6-7 days and approximately 1-2 days, respectively. The plasma half-lives of thyroxine and triiodothyronine are decreased in patients with hyperthyroidism and increased in those with hypothyroidism.

Toxicity Summary
IDENTIFICATION AND USE: Levothyroxine occurs as crystals or needles. As a drug, levothyroxine sodium is used as replacement or supplemental therapy in congenital or acquired hypothyroidism. It is also used in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. The injection form of levothyroxine sodium is indicated for the treatment of myxedema coma. Levothyroxine has also been used in veterinary medicine. HUMAN EXPOSURE AND TOXICITY: The signs and symptoms of levothyroxine overdosage are those of hyperthyroidism. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Studies indicate that careful attention is necessary when initiating the administration of levothyroxine sodium to very-low-birth-weight infants. Ingestion of levothyroxine in children typically follows a benign course, but overdose can result in significant complications, including seizures and arrhythmias, both of which should be monitored for. In one genotoxicity study, the ability of thyroxine to induce sister chromatid exchange and micronuclei was tested in cultured human lymphocytes. Thyroxine exhibited weak clastogenic effects only at high concentrations. ANIMAL STUDIES: A single acute overdose in small animals is less likely to cause severe thyrotoxicosis than chronic overdosage. Vomiting, diarrhea, transition from hyperactivity to lethargy, hypertension, tachycardia, tachypnea, dyspnea, and abnormal pupillary light reflexes may be noted in dogs and cats. In dogs, clinical signs may appear within 1-9 hours after ingestion. Four pregnant New Zealand white rabbits received intramuscular levothyroxine at 250 ug/kg on days 25 and 26 of gestation. Maternal and fetal plasma-free levothyroxine concentration was higher than in controls, with the highest concentration noted at 14 days of neonatal period. Treatment resulted in fetal hyperglycemia and depletion of fetal liver glycogen content. Animal studies have not been performed to evaluate levothyroxine carcinogenic potential, mutagenic potential or effects on fertility.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Levothyroxine (T4) is a normal component of human milk. Limited data on exogenous replacement doses of levothyroxine during breastfeeding indicate no adverse effects in infants. The American Thyroid Association recommends that subclinical and overt hypothyroidism should be treated with levothyroxine in lactating women seeking to breastfeed. Adequate levothyroxine treatment during lactation may normalize milk production in hypothyroid lactating mothers with low milk supply. Levothyroxine dosage requirement may be increased in the postpartum period compared to prepregnancy requirements in patients with Hashimoto's thyroiditis.
◉ Effects in Breastfed Infants
Effects of exogenous thyroid hormone administration to mothers on their infant have not been reported. One case of apparent mitigation of cretinism in hypothyroid infants by breastfeeding has been reported, but the amounts of thyroid hormones in milk are not optimal, and this result has been disputed. The thyroid hormone content of human milk from the mothers of very preterm infants appears not to be sufficient to affect the infants' thyroid status. The amounts of thyroid hormones in milk are apparently not sufficient to interfere with diagnosis of hypothyroidism.
In a telephone follow-up study, 5 nursing mothers reported taking levothyroxine (dosage unspecified). The mothers reported no adverse reactions in their infants.
One mother who had undergone a thyroidectomy was taking levothyroxine 100 mcg daily as well as calcium carbonate and calcitriol. Her breastfed infant was reportedly "thriving" at 3 months of age.
A woman with propionic acidemia took levothyroxine 50 mcg daily as well as biotin, carnitine, and various amino acids while exclusively breastfeeding her infant for 2 months and nonexclusively for 10 months. At that time, the infant had normal growth and development.
◉ Effects on Lactation and Breastmilk
Adequate thyroid hormone serum levels are required for normal lactation. Replacing deficient thyroid levels should improve milk production caused by hypothyroidism. Supraphysiologic doses would not be expected to further improve lactation.

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Protein Binding
Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA) and albumin (TBA). The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone where only unbound hormone is metabolically active.

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Interactions
Antacids (e.g., aluminum hydroxide, magnesium hydroxide, calcium carbonate), simethicone, and sucralfate bind thyroid agents in the GI tract and delay or prevent their absorption. Calcium carbonate may form an insoluble chelate with levothyroxine, resulting in decreased levothyroxine absorption and increased serum thyrotropin concentrations; in vitro studies indicate that levothyroxine binds to calcium carbonate at acidic pH levels. To minimize or prevent this interaction, some clinicians recommend that these agents be administered approximately 4 hours apart when the drugs must be used concurrently with thyroid agents.
Serum concentrations of digitalis glycosides may be decreased in patients with hyperthyroidism or in patients with hypothyroidism in whom a euthyroid state has been achieved. Thus, therapeutic effects of digitalis glycosides may be reduced in these patients.
Drugs that induce hepatic microsomal enzymes (e.g., carbamazepine, phenytoin, phenobarbital, rifampin) may accelerate metabolism of thyroid agents, resulting in increased thyroid agent dosage requirements. Phenytoin and carbamazepine also reduce serum protein binding of levothyroxine, and total- and free-T4 may be reduced by 20-40%, but most patients have normal serum concentrations of thyrotropin (thyroid-stimulating hormone, TSH) and are clinically euthyroid. /Thyroid agents/
Bile acid sequestrants (e.g., cholestyramine resin, colestipol) bind thyroid agents in the GI tract and substantially impair their absorption. In vitro studies indicate that the binding is not readily reversible. To minimize or prevent this interaction, these agents should be administered at least 4 hours apart when the drugs must be used concurrently.
For more Interactions (Complete) data for LEVOTHYROXINE (14 total), please visit the HSDB record page.

[1]. Arici M, et al. Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients. Endocr J. 2018 Mar 28;65(3):317-323.
[2]. Corriveau S, et al. Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animalmodel. J Clin Transl Endocrinol. 2015 Sep 9;2(4):144-149

Therapeutic Uses
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Levothyroxine is included in the database.
Levothyroxine sodium is used ... as replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. Specific indications include: primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism and subclinical hypothyroidism. Primary hypothyroidism may result from functional deficiency, primary atrophy, partial or total congenital absence of the thyroid gland, or from the effects of surgery, radiation, or drugs, with or without the presence of goiter. /Included in US product label/
Levothyroxine sodium is used ... in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. /Included in US product label/
Levothyroxine Sodium for Injection is indicated for the treatment of myxedema coma. Important Limitations of Use: The relative bioavailability between Levothyroxine Sodium for Injection and oral levothyroxine products has not been established. Caution should be used when switching patients from oral levothyroxine products to Levothyroxine Sodium for Injection as accurate dosing conversion has not been studied. /Included in US product label/
For more Therapeutic Uses (Complete) data for LEVOTHYROXINE (6 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS. Thyroid hormones, including Levothyroxine Sodium for Injection, should not be used for the treatment of obesity or for weight loss. Larger doses may produce serious or even life threatening manifestations of toxicity.
/BOXED WARNING/ WARNING: Thyroid hormones, including Synthroid, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.
Excessive bolus dosing of Levothyroxine Sodium for Injection (greater than 500 ug) are associated with cardiac complications, particularly in the elderly and in patients with an underlying cardiac condition. Adverse events that can potentially be related to the administration of large doses of Levothyroxine Sodium for Injection include arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death. Cautious use, including doses in the lower end of the recommended range, may be warranted in these populations. Close observation of the patient following the administration of Levothyroxine Sodium for Injection is advised.
Studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of thyroid hormones in children. However, caution is necessary in interpreting results of thyroid function tests in neonates, because serum T4 concentrations are transiently elevated and serum T4 concentrations are transiently low, and the infant pituitary is relatively insensitive to the negative feedback effect of thyroid hormones. /Thyroid hormones/
For more Drug Warnings (Complete) data for LEVOTHYROXINE (17 total), please visit the HSDB record page.

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Pharmacodynamics
Oral levothyroxine is a synthetic hormone that exerts the same physiologic effect as endogenous T₄, thereby maintaining normal T₄ levels when a deficiency is present. Levothyroxine has a narrow therapeutic index and is titrated to maintain a euthyroid state with TSH (thyroid stimulating hormone) within a therapeutic range of 0.4–4.0 mIU/L. Over- or under-treatment with levothyroxine may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function and glucose and lipid metabolism. The dose of levothyroxine should be titrated slowly and carefully and patients should be monitored for their response to titration to avoid these effects. TSH levels should be monitored at least yearly to avoid over-treating with levothyroxine which can result in hyperthyroidism (TSH <0.1mIU/L) and symptoms of increased heart rate, diarrhea, tremor, hypercalcemia, and weakness to name a few. As many cardiac functions including heart rate, cardiac output, and systemic vascular resistance are closely linked to thyroid status, over-treatment with levothyroxine may result in increases in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients. In populations with any cardiac concerns, levothyroxine should be initiated at lower doses than those recommended in younger individuals or in patients without cardiac disease. Patients receiving concomitant levothyroxine and sympathomimetic agents should be monitored for signs and symptoms of coronary insufficiency. If cardiac symptoms develop or worsen, reduce the levothyroxine dose or withhold for one week and restart at a lower dose. Increased bone resorption and decreased bone mineral density may occur as a result of levothyroxine over-replacement, particularly in post-menopausal women. The increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorous, elevations in bone alkaline phosphatase and suppressed serum parathyroid hormone levels. Administer the minimum dose of levothyroxine that achieves the desired clinical and biochemical response to mitigate this risk. Addition of levothyroxine therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing or discontinuing levothyroxine.

C15H11I4NO4

776.8700

776.686

C, 23.19; H, 1.43; I, 65.34; N, 1.80; O, 8.24

51-48-9

Thyroxine sulfate;77074-49-8;L-Thyroxine sodium salt pentahydrate;6106-07-6;L-Thyroxine sodium;55-03-8;L-Thyroxine-13C6-1;1217780-14-7;Biotin-(L-Thyroxine);149734-00-9;Biotin-hexanamide-(L-Thyroxine);2278192-78-0;Thyroxine hydrochloride-13C6;1421769-38-1;L-Thyroxine-13C6;720710-30-5;L-Thyroxine-13C6,15N;1431868-11-9

5819

Crystals
Needles

2.6±0.1 g/cm3

576.3±50.0 °C at 760 mmHg

235 °C

302.3±30.1 °C

0.0±1.7 mmHg at 25°C

1.795

5.93

92.78

3

5

5

24

420

1

IC1C(=C(C([H])=C(C=1[H])C([H])([H])[C@@]([H])(C(=O)O[H])N([H])[H])I)OC1C([H])=C(C(=C(C=1[H])I)O[H])I

XUIIKFGFIJCVMT-LBPRGKRZSA-N

InChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1

(S)-2-amino-3-(4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)propanoic acid

L-Thyroxin, L Thyroxin, T4, Levothyroxine sodium, Levothyroxine sodium pentahydrate, Thyroxine; L-thyroxine; 51-48-9; thyroxine; thyroxin; Levothyroxin; Tetraiodothyronine; 3,3',5,5'-Tetraiodo-L-thyronine;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~321.80 mM)
1M NaOH : 5 mg/mL (~6.44 mM)
H2O : < 0.1 mg/mL

配方 1 中的溶解度: ≥ 2.08 mg/mL (2.68 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (2.68 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (2.68 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。