Absorption, Distribution and Excretion
The peak plasma concentration (Cmax) of amiodarone is typically reached 3 to 7 hours after administration. Following a single intravenous dose of amiodarone, the onset of action is generally 1 to 30 minutes, with therapeutic effects lasting 1 to 3 hours. The steady-state plasma concentration of amiodarone ranges from 0.4 to 11.99 μg/ml; for patients with arrhythmias, it is recommended to maintain a steady-state concentration between 1.0 and 2.5 μg/ml. It is noteworthy that the onset of action of amiodarone may sometimes begin after 2 to 3 days, but typically takes 1 to 3 weeks, even with a high loading dose. The bioavailability of amiodarone varies in clinical studies, averaging between 35% and 65%. Food Effects: In healthy subjects, a single 600 mg dose of amiodarone administered immediately after consuming a high-fat diet resulted in a 2.3-fold increase in AUC and a 3.8-fold increase in Cmax. Food also enhances absorption, reducing Tmax by approximately 37%. Amiodarone is primarily eliminated through hepatic metabolism and bile excretion. Small amounts of desethylamiodarone (DEA) can be detected in urine. In a pharmacokinetic study of 3 healthy individuals and 3 patients with supraventricular tachycardia (SVT), the volume of distribution (VOD) ranged from 9.26 to 17.17 L/kg in healthy volunteers and from 6.88 to 21.05 L/kg in SVT patients. Prescribing information indicates significant individual variability in the VOD of amiodarone, with an average VOD of approximately 60 L/kg. Amiodarone accumulates systemically, particularly in adipose tissue and highly vascularized organs, including the lungs, liver, and spleen. The major metabolite of amiodarone, desethylamiodarone (DEA), is present in higher concentrations in the same tissues as amiodarone. A clinical study showed that the clearance rate of amiodarone after intravenous administration was 220 to 440 ml/hr/kg in patients with ventricular fibrillation and ventricular tachycardia. Another study determined that the systemic clearance of amiodarone after a single intravenous injection ranged from 0.10 to 0.77 L/min. Renal impairment did not appear to affect amiodarone clearance, but hepatic impairment may have reduced it. Patients with cirrhosis showed significantly reduced peak DEA plasma concentrations (Cmax) and mean amiodarone concentrations, but no significant change in amiodarone plasma concentrations. Severe left ventricular dysfunction prolongs the half-life of DEA. Regarding monitoring: There are currently no guidelines for adjusting amiodarone dosage in patients with renal, hepatic, or cardiac abnormalities. Close clinical monitoring is recommended for patients receiving long-term amiodarone treatment, especially elderly patients and those with severe left ventricular dysfunction. Metabolism/Metabolites: This drug is metabolized by CYP3A4 and CYP2C8 enzymes to the major metabolite, desethylamiodarone (DEA). CYP3A4 enzymes are present in the liver and intestine. Hydroxyl metabolites of DEA have been identified in mammals, but their clinical significance remains unclear. Amiodarone's known metabolites include N-deethylamiodarone. Amiodarone is primarily metabolized in the liver via CYP2C8 (less than 1% of the unchanged drug is found in urine) and may affect the metabolism of several other drugs. The major metabolite of amiodarone is deethylamiodarone (DEA), which also has antiarrhythmic effects. Grapefruit juice inhibits amiodarone metabolism, leading to elevated serum amiodarone levels. Elimination pathway: Amiodarone is primarily eliminated via hepatic metabolism and bile excretion; very little amiodarone or DEA is excreted in urine. Half-life: 58 days (range 15-142 days). The terminal half-life of amiodarone varies from patient to patient, but is generally long, ranging from approximately 9-100 days. Half-life data vary depending on the source. According to amiodarone's prescribing information, the mean apparent plasma terminal elimination half-life of amiodarone is 58 days (range 15 to 142 days). The terminal half-life of the active metabolite (DEA) ranges from 14 to 75 days. One study showed that the plasma half-life of amiodarone after a single dose ranged from 3.2 to 79.7 hours.

Toxicity Summary
The antiarrhythmic effect of amiodarone can be attributed to at least two main mechanisms. It prolongs the duration of the cardiomyocyte action potential (phase 3) and the refractory period, and acts as a non-competitive α and β adrenergic inhibitor. Toxicity Data
Intravenous injection, mice: LD50 = 178 mg/kg.

[1]. Singh, B.N. and E.M. Vaughan Williams, The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol, 1970. 39(4): p. 657-67.

[2]. Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol, 1976. 38(7): p. 934-44.

Pharmacodynamics
Intravenous amiodarone relaxes vascular smooth muscle, reduces peripheral vascular resistance (afterload), and slightly increases cardiac index. This route of administration can also reduce cardiac conduction, thereby preventing and treating arrhythmias. However, oral amiodarone does not cause significant changes in left ventricular ejection fraction. Similar to other antiarrhythmic drugs, controlled clinical trials have not demonstrated that oral amiodarone improves survival. Amiodarone prolongs QRS duration and QT interval. Furthermore, it reduces sinoatrial node automaticity and atrioventricular node conduction velocity. The automaticity of ectopic pacemakers is also suppressed. Because amiodarone contains a high concentration of iodine, it can interfere with normal thyroid function; therefore, taking amiodarone may also lead to thyrotoxicosis or hypothyroidism.

C25H29I2NO3

645.31

645.024

1951-25-3

Amiodarone-d10 hydrochloride;1261393-77-4;Amiodarone hydrochloride;19774-82-4;Amiodarone-d4 hydrochloride;1216715-80-8

2157

Colorless to light yellow oil

1.58 g/cm3

635.1ºC at 760 mmHg

156ºC

337.9ºC

4.95E-16mmHg at 25°C

6.936

0

4

11

31

547

0

CCCCC1=C(C(C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)=O)C3=C(O1)C=CC=C3

IYIKLHRQXLHMJQ-UHFFFAOYSA-N

InChI=1S/C25H29I2NO3/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

(2-butyl-1-benzofuran-3-yl)-[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]methanone

Amiodaronum AratacCordarone Amiodarona Nexterone

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)