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Amiodarone HCl (NSC 85442)

Alias:
Cat No.:V1672 Purity: ≥98%
Amiodarone HCl(formerly NSC-85442; NSC85442;NSC 85442; Cordarone),the hydrochloride salt of amiodarone, is an antiarrhythmic drugused to treat and prevent an irregular heartbeat.
Amiodarone HCl (NSC 85442)
Amiodarone HCl (NSC 85442) Chemical Structure CAS No.: 19774-82-4
Product category: Potassium Channel
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
2g
5g
10g
100g
Other Sizes

Other Forms of Amiodarone HCl (NSC 85442):

  • Amiodarone-d4 hydrochloride
  • Amiodarone
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Amiodarone HCl (formerly NSC-85442; NSC85442; NSC 85442; Cordarone), the hydrochloride salt of amiodarone, is an antiarrhythmic drug used to treat and prevent an irregular heartbeat. It acts as a sodium/potassium-ATPase inhibitor and an autophagy activator used to treat various types of cardiac dysrhythmias.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
Amiodarone hydrochloride inhibits the inward IhERG tail with an IC50 of 117.8 nM in 94 mM high-K+ external solution ([K+]e) [1]. Amiodarone hydrochloride (1 μM) blocks inwardIhERG by 68.8±6.1%, and concentration response data gave IC50 with h values of 765.5±287.8 nM and 0.9±0.4 for T623A hERG [1]. Amiodarone (1 μM) blocks inward IhERG with IC50 and h values of 979.2±84.3 nM and 1.1±0.1 for S624A hERG [1]. Amiodarone (1-6 μg/mL) promotes cell proliferation in human embryonic lung fibroblasts (HELFs), while PD98059 or SB203580 decreases this action [2]. Amiodarone (1-6 μg/mL) does not induce apoptosis in HELFs cells. Amiodarone hydrochloride (greater than 15 μg/mL) causes apoptosis [2]. Amiodarone hydrochloride (1, 3 and 6 μg/mL; 24 hours) stimulates α-SMA and vimentin mRNA and protein expression associated by an increase in ERK1/2 and p38 MAPK phosphorylation [2].
ln Vivo
Animal models of pulmonary fibrosis can be created with the use of amiodarone hydrochloride in animal modeling. Chronic administration of 90 and 180 mg/kg/day of amiodarone hydrochloride causes a dose-dependent modification of ion channel expression, which is correlated with the drug's effects on cardiac electrophysiology [3].
Cell Assay
Cell Proliferation Assay[2]
Cell Types: HELFs
Tested Concentrations: 1, 3 and 6 μg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: Increased HELFs proliferation compared with the control group.

Western Blot Analysis[2]
Cell Types: HELFs
Tested Concentrations: 1, 3 and 6 μg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: α-SMA and vimentin were increased Dramatically in a dose-dependent manner.

RT-PCR[2]
Cell Types: HELFs
Tested Concentrations: 1, 3 and 6 μg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: Induced an increase of α-SMA and vimentin mRNA expression.
Animal Protocol
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.
ADME/Pharmacokinetics
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.
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)
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/Toxicokinetics
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.
Toxicity Data
Intravenous, mouse: LD50 = 178 mg/kg.
References
[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.
Additional Infomation
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.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C25H29I2NO3.HCL
Molecular Weight
681.77
Exact Mass
681
CAS #
19774-82-4
Related CAS #
Amiodarone-d4 hydrochloride;1216715-80-8;Amiodarone;1951-25-3
PubChem CID
2157
Appearance
White to off-white solid powder
Density
1.58 g/cm3
Boiling Point
635.1ºC at 760 mmHg
Melting Point
154-158°C
Flash Point
337.9ºC
LogP
7.738
Hydrogen Bond Donor Count
0
Hydrogen Bond Acceptor Count
4
Rotatable Bond Count
11
Heavy Atom Count
31
Complexity
547
Defined Atom Stereocenter Count
0
InChi Key
ITPDYQOUSLNIHG-UHFFFAOYSA-N
InChi Code
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
Chemical Name
2-Butyl-3-benzofuryl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone hydrochloride
Synonyms

NSC 85442; Amiodarone hydrochloride;NSC-85442; NSC85442;

HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO:23 mg/mL (33.7 mM)
Water:<1 mg/mL
Ethanol: 11 mg/mL (16.1 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (3.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.4668 mL 7.3339 mL 14.6677 mL
5 mM 0.2934 mL 1.4668 mL 2.9335 mL
10 mM 0.1467 mL 0.7334 mL 1.4668 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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g/mol

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
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Clinical Trial Information
Evaluation of Cardioverter Capacity of Amiodarone Pre-electrical Cardioversion in Persistent Atrial Fibrillation
CTID: NCT06645249
Phase: Phase 4    Status: Not yet recruiting
Date: 2024-12-02
Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation After Cardiac Surgery
CTID: NCT01422148
Phase: Phase 2    Status: Not yet recruiting
Date: 2024-08-06
Nifekalant Versus Amiodarone in New-Onset Atrial Fibrillation After Cardiac Surgery
CTID: NCT05169866
Phase: Phase 3    Status: Recruiting
Date: 2024-06-03
Vernakalant Versus Amiodarone for Post-operative Atrial Fibrillation in Cardiac Surgery Patients
CTID: NCT04748991
Phase: Phase 3    Status: Not yet recruiting
Date: 2024-05-22
Amiodarone and N-Acetylcysteine or Amiodarone Alone for Preventing Atrial Fibrillation After Thoracic Surgery
CTID: NCT02750319
Phase: Phase 3    Status: Active, not recruiting
Date: 2024-05-16
View More

MAGNAM Trial, Magnesium Versus Amiodarone in Atrial Fibrillation in Critical Care
CTID: NCT05287191
Phase: Phase 3    Status: Recruiting
Date: 2024-04-25


Effectiveness of Repeated Amiodarone Dosing Regimen Versus Standard Dosing Regimen in Atrial Fibrillation Patient With Rapid Ventricular Response
CTID: NCT06262932
Phase: Phase 4    Status: Not yet recruiting
Date: 2024-04-08
AMSA and Amiodarone Study in Cardiac Arrest
CTID: NCT04997980
Phase:    Status: Completed
Date: 2024-03-08
Pragmatic Amiodarone Trial to Reduce Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery
CTID: NCT05543278
Phase: Phase 4    Status: Not yet recruiting
Date: 2024-01-23
Prevention of Postop Atrial Fibrillation Through Intraoperative Inducibility of Atrial Fibrillation and Amiodarone Treatment
CTID: NCT03868150
Phase: Phase 4    Status: Recruiting
Date: 2023-11-22
Repeated Amiodarone Dosing In Cardiac surgicaL Procedures
CTID: NCT05004077
Phase: Phase 4    Status: Terminated
Date: 2023-11-18
Evaluate the Pharmacokinetics and Safety of MK-4448 in Participants With Nonvalvular Atrial Fibrillation or Atrial Flutter
CTID: NCT01229254
Phase: Phase 2    Status: Completed
Date: 2023-08-07
Prophylaxis for Patients at Risk to Eliminate Post-operative Atrial Fibrillation
CTID: NCT04392921
Phase: N/A    Status: Recruiting
Date: 2023-03-29
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Catheter ablation versus Amiodarone to pRevent Future ventricular tachycardia Episodes in patients with a defibrillator and a history of a myocardial infarction
CTID: null
Phase: Phase 4    Status: Prematurely Ended
Date: 2011-04-28
Catheter ablation versus Amiodarone to prevent future shock episodes in patients with a defibrillator and a history of a myocardial infarction.
CTID: null
Phase: Phase 4    Status: Prematurely Ended
Date: 2010-03-18
Double blind placebo controlled dose ranging study of the efficacy and safety of celivarone at 50, 100 or 300 mg OD with Amiodarone as calibrator for the prevention of ICD interventions or death.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2009-09-21
Estudio de Ablación vs fármacos Antiarrítmicos en Fibrilacion Auricular Persistente (SARA)
CTID: null
Phase: Phase 4    Status: Ongoing
Date: 2009-02-06
Amiodarone prophylaxis for atrial fibrillation in patients undergoing surgery for lung cancer: A controlled, randomized, double blinded trial.
CTID: null
Phase: Phase 4    Status: Completed
Date: 2008-03-11
Randomized double blind trial to evaluate the efficacy and safety of dronedarone (400 mg BID) versus amiodarone (600 mg daily for 28 days then 200 mg daily thereafter) for at least 6 months for the maintenance of sinus rhythm in patients with atrial fibrillation (AF)
CTID: null
Phase: Phase 3    Status: Completed
Date: 2007-04-11
Intravenöösi metoproli versus amiodaroni sydänleikkauksen jälkeisen eteisvärinän estossa: vertaileva tutkimus tehosta, sivuvaikutuksista ja kustannuksista
CTID: null
Phase: Phase 4    Status: Ongoing
Date: 2006-10-06
Duration of Amiodarone therapy required for new post cardiac surgery atrial fibrillation.
CTID: null
Phase: Phase 4    Status: Prematurely Ended
Date: 2005-02-21
Placebo controlled double blind dose ranging study of the efficacy and safety of SSR149744C 50, 100, 200, or 300 mg OD, with amiodarone as calibrator for the maintenance of sinus rhythm in patients with recent atrial fibrillation/flutter.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2004-12-20
RANDOMIZED COMPARISON OF CIRCUMFERENTIAL PULMONARY VEIN ABLATION VERSUS ANTIARRHYTHMIC THERAPY FOR CURING PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION. (APAF STUDY)
CTID: null
Phase: Phase 4    Status: Completed
Date: 2004-11-12

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