Amiodarone HydroHClide 抑制内向 IhERG 尾部，在 94 mM 高 K+ 外部溶液 ([K+]e) 中的 IC50 为 117.8 nM [1]。盐酸胺碘酮 (1 μM) 向内阻断 IhERG 68.8±6.1%，浓度响应数据给出的 IC50 值为 765.5±287.8 nM，对于 T623A hERG 为 0.9±0.4 [1]。胺碘酮 (1 μM) 阻断内向 IhERG，IC50 和 h 值为 979.2±84.3 nM，S624A hERG 为 1.1±0.1 [1]。胺碘酮 (1-6 μg/mL) 促进人胚胎肺成纤维细胞 (HELF) 的细胞增殖，而 PD98059 或 SB203580 会减弱这种作用 [2]。胺碘酮 (1-6 μg/mL) 不会诱导 HELF 细胞凋亡。盐酸胺碘酮（大于 15 μg/mL）会导致细胞凋亡 [2]。胺碘酮盐酸盐（1、3 和 6 μg/mL；24 小时）通过 ERK1/2 和 p38 MAPK 磷酸化的增加刺激 α-SMA 和波形蛋白 mRNA 和蛋白表达 [2]。

在动物模型中使用盐酸胺碘酮可以建立肺纤维化的动物模型。长期服用 90 和 180 mg/kg/天的盐酸胺碘酮会引起离子通道表达的剂量依赖性改变，这与药物对心脏电生理学的影响相关 [3]。

细胞增殖测定[2]
细胞类型： HELF
测试浓度： 1、3 和 6 μg/mL
孵育时间： 24小时
实验结果：与对照组相比，HELF增殖增加。

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蛋白质印迹分析[2]
细胞类型： HELF
测试浓度： 1、3 和 6 µg/mL
孵育持续时间：24小时
实验结果：α-SMA和波形蛋白以剂量依赖性方式显着增加。

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RT-PCR[2]
细胞类型： HELF
测试浓度： 1、3 和 6 μg/mL
孵育持续时间：24小时
实验结果：诱导α-SMA和波形蛋白mRNA表达增加。

Animal/Disease Models: Tenweeks old male C57BL/6 mice[3]
Doses: 30, 90, and 180 mg/kg/day
Route of Administration: Treated po (oral gavage) for 6 weeks
Experimental Results: Mice treated with 90 and 180 mg/kg/day had diminished body and heart weights, although their heart weight-to-body weight ratios were not Dramatically different from sham. 6-week treatment induced a decrease in plasma triiodothyronine and an increase in reverse triiodothyronine. This effect reached significance for the 90 and 180 but not for the 30 mg/kg/day dose groups.

Absorption, Distribution and Excretion
The Cmax of amiodarone in the plasma is achieved about 3 to 7 hours after administration. The general time to onset of action of amiodarone after one dose given by the intravenous route is between 1 and 30 minutes, with therapeutic effects lasting from 1-3 hours. Steady-state concentrations of amiodarone in the plasma ranges between 0.4 to 11.99 μg/ml; it is advisable that steady-state levels are generally maintained between 1.0 and 2.5 μg/ml in patients with arrhythmias. Interestingly, its onset of action may sometimes begin after 2 to 3 days, but frequently takes 1 to 3 weeks, despite the administration of higher loading doses. The bioavailability of amiodarone varies in clinical studies, averaging between 35 and 65%. Effect of food In healthy subjects who were given a single 600-mg dose immediately after consuming a meal high in fat, the AUC of amiodarone increased by 2.3 and the Cmax by 3.8 times. Food also enhances absorption, reducing the Tmax by about 37%.
Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion. A small amount of desethylamiodarone (DEA) is found in the urine.
In a pharmacokinetic study of 3 healthy individuals and 3 patients diagnosed with supraventricular tachycardia (SVT), the volume of distribution was found to be 9.26-17.17 L/kg in healthy volunteers and 6.88-21.05 L/kg in the SVT patients. Prescribing information mentions that the volume of distribution of amiodarone varies greatly, with a mean distribution of approximately 60 L/kg. It accumulates throughout the body, especially in adipose tissue and highly vascular organs including the lung, liver, and spleen. One major metabolite of amiodarone, desethylamiodarone (DEA), is found in even higher proportions in the same tissues as amiodarone.
The clearance of amiodarone after intravenous administration in patients with ventricular fibrillation and ventricular tachycardia ranged from 220 to 440 ml/hr/kg in one clinically study. Another study determined that the total body clearance of amiodarone varies from 0.10 to 0.77 L/min after one intravenous dose. Renal impairment does not appear to affect the clearance of amiodarone, but hepatic impairment may reduce clearance. Patients with liver cirrhosis exhibited significantly lower Cmax and mean amiodarone concentration for DEA, but not for amiodarone. Severe left ventricular dysfunction prolongs the half-life of DEA. A note on monitoring No guidelines have been developed for adjusting the dose of amiodarone in renal, hepatic, or cardiac abnormalities. In patients on chronic amiodarone treatment, close clinical monitoring is advisable, especially for elderly patients and those with severe left ventricular dysfunction.

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Metabolism / Metabolites
This drug is metabolized to the main metabolite desethylamiodarone (DEA) by the CYP3A4 and CYP2C8 enzymes. The CYP3A4 enzyme is found in the liver and intestines. A hydroxyl metabolite of DEA has been identified in mammals, but its clinical significance is unknown.
Amiodarone has known human metabolites that include N-Desethylamiodarone.
Amiodarone is extensively metabolized in the liver via CYP2C8 (under 1% unchanged in urine), and can effect the metabolism of numerous other drugs. The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties. The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone.
Route of Elimination: Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine.
Half Life: 58 days (range 15-142 days)

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Biological Half-Life
The terminal half-life of amiodarone varies according to the patient, but is long nonetheless, and ranges from about 9-100 days. The half-life duration varies according to different sources. According to the prescribing information for amiodarone, the average apparent plasma terminal elimination half-life of amiodarone is of 58 days (ranging from 15 to 142 days). The terminal half-life range was between 14 to 75 days for the active metabolite, (DEA). The plasma half-life of amiodarone after one dose ranges from 3.2 to 79.7 hours, according to one source.

Toxicity Summary
The antiarrhythmic effect of amiodarone may be due to at least two major actions. It prolongs the myocardial cell-action potential (phase 3) duration and refractory period and acts as a noncompetitive a- and b-adrenergic inhibitor.

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Toxicity Data
Intravenous, mouse: LD₅₀ = 178 mg/kg.

[1]. Yihong Zhang,et al. Interactions between amiodarone and the hERG potassium channel pore determined with mutagenesis and in silico docking. Biochem Pharmacol. 2016 Aug 1;113:24-35.
[2]. Jie Weng, et al. Amiodarone induces cell proliferation and myofibroblast differentiation via ERK1/2 and p38 MAPK signaling in fibroblasts. Biomed Pharmacother. 2019 Jul;115:108889.
[3]. Sabrina Le Bouter, et al. Long-term amiodarone administration remodels expression of ion channel transcripts in the mouse heart. Circulation. 2004 Nov 9;110(19):3028-35.

Pharmacodynamics
After intravenous administration, amiodarone acts to relax smooth muscles that line vascular walls, decreases peripheral vascular resistance (afterload), and increases the cardiac index by a small amount. Administration by this route also decreases cardiac conduction, preventing and treating arrhythmias. When it is given orally, however, amiodarone does not lead to significant changes in the left ventricular ejection fraction. Similar to other anti-arrhythmic agents, controlled clinical trials do not confirm that oral amiodarone increases survival. Amiodarone prolongs the QRS duration and QT interval. In addition, a decreased SA (sinoatrial) node automaticity occurs with a decrease in AV node conduction velocity. Ectopic pacemaker automaticity is also inhibited. Thyrotoxicosis or hypothyroidism may also result from the administration of amiodarone, which contains high levels of iodine, and interferes with normal thyroid function.

C25H29I2NO3.HCL

681.77

681

19774-82-4

Amiodarone-d4 hydrochloride;1216715-80-8;Amiodarone;1951-25-3

2157

White to off-white solid powder

1.58 g/cm3

635.1ºC at 760 mmHg

154-158°C

337.9ºC

7.738

42.68

0

4

11

31

547

0

ITPDYQOUSLNIHG-UHFFFAOYSA-N

InChI=1S/C25H29I2NO3.ClH/c1-4-7-11-22-23(18-10-8-9-12-21(18)31-22)24(29)17-15-19(26)25(20(27)16-17)30-14-13-28(5-2)6-3;/h8-10,12,15-16H,4-7,11,13-14H2,1-3H3;1H

2-Butyl-3-benzofuryl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

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

配方 1 中的溶解度: ≥ 2.5 mg/mL (3.67 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 25.0 mg/mL澄清DMSO储备液加入到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: ≥ 2.5 mg/mL (3.67 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 25.0 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: ≥ 2.5 mg/mL (3.67 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 25.0 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。