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药品详细

Amiodarone(胺碘酮)

化学结构式图
中文名
胺碘酮
英文名
Amiodarone
分子式
C25H29I2NO3
化学名
(2-{4-[(2-butyl-1-benzofuran-3-yl)carbonyl]-2,6-diiodophenoxy}ethyl)diethylamine
分子量
Average: 645.3116
Monoisotopic: 645.023680639
CAS号
1951-25-3
ATC分类
C01B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [PubChem]

生产厂家
  • Akorn inc
  • Apotex corp
  • App pharmaceuticals llc
  • Aurosal pharmaceuticals llc
  • Barr laboratories inc
  • Bedford laboratories
  • Bedford laboratories div ben venue laboratories inc
  • Ben venue laboratories inc
  • Bioniche pharma usa llc
  • Claris lifesciences ltd
  • Gland pharma ltd
  • Hikma farmaceutica (portugal) sa
  • Hospira inc
  • International medication systems ltd
  • Mylan pharmaceuticals inc
  • Prism pharmaceuticals inc
  • Sandoz inc
  • Taro pharmaceuticals usa inc
  • Teva parenteral medicines inc
  • Teva pharmaceuticals usa
  • Teva pharmaceuticals usa inc
  • Upsher smith laboratories inc
  • Wockhardt ltd
  • Wyeth pharmaceuticals inc
  • Zydus pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. DELTOUR G, BINON F, TONDEUR R, GOLDENBERG C, HENAUX F, SION R, DERAY E, CHARLIER R: [Studies in the benzofuran series. VI. Coronary-dilating activity of alkylated and aminoalkylated derivatives of 3-benzoylbenzofuran.] Arch Int Pharmacodyn Ther. 1962 Sep 1;139:247-54. Pubmed
  2. CHARLIER R, DELTOUR G, TONDEUR R, BINON F: [Studies in the benzofuran series. VII. Preliminary pharmacological study of 2-butyl-3-(3,5-diiodo-4-beta-N-diethylaminoethoxybenzoyl)-benzofuran.] Arch Int Pharmacodyn Ther. 1962 Sep 1;139:255-64. Pubmed
  3. Singh BN, Vaughan Williams EM: The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol. 1970 Aug;39(4):657-67. Pubmed
  4. Rosenbaum MB, Chiale PA, Halpern MS, Nau GJ, Przybylski J, Levi RJ, Lazzari JO, Elizari MV: Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol. 1976 Dec;38(7):934-44. Pubmed
  5. Rosenbaum MB, Chiale PA, Haedo A, Lazzari JO, Elizari MV: Ten years of experience with amiodarone. Am Heart J. 1983 Oct;106(4 Pt 2):957-64. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Benzofurans
  • Phenols and Derivatives
  • Ethers
  • Anisoles
  • Benzoyl Derivatives
Substructures
  • Benzofurans
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Halobenzenes
  • Furans
  • Benzoyl Derivatives
  • Phenyl Esters
  • Ketones
适应症
药理
Indication Intravenously, for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy. Orally, for the treatment of life-threatening recurrent ventricular arrhythmias such as recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia.
Pharmacodynamics Amiodarone belongs to a class of drugs called Vaughan-Williams Class III antiarrhythmic agents. It is used in the treatment of a wide range of cardiac tachyarhthmias, including both ventricular and supraventricular (atrial) arrhythmias. After intravenous administration in man, amiodarone relaxes vascular smooth muscle, reduces peripheral vascular resistance (afterload), and slightly increases cardiac index. Amiodarone prolongs phase 3 of the cardiac action potential. It has numerous other effects however, including actions that are similar to those of antiarrhythmic classes Ia, II, and IV. Amiodarone shows beta blocker-like and calcium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects.
Mechanism of action 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.
Absorption Slow and variable (about 20 to 55% of an oral dose is absorbed).
Volume of distribution Not Available
Protein binding >96%
Metabolism
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Amiodarone
N-desethylamiodarone Details
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)
Clearance
  • 90-158 mL/h/kg [Healthy with a single dose IV (5 mg/kg over 15 min)]
  • 100 mL/h/kg [Normal subjects > 65 yrs]
  • 150 mL/h/kg [younger subjects]
  • 220 and 440 mL/h/kg [patients with VT and VF]
Toxicity Intravenous, mouse: LD50 = 178 mg/kg. Some side effects have a significant mortality rate: specifically, hepatitis, exacerbation of asthma and congestive failure, and pneumonitis.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
water solubility Low Not Available
logP 7.57 AVDEEF,A (1997)
Predicted Properties
Property Value Source
water solubility 4.76e-03 g/l ALOGPS
logP 7.24 ALOGPS
logP 7.64 ChemAxon
logS -5.1 ALOGPS
pKa (strongest basic) 8.47 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 42.68 ChemAxon
rotatable bond count 11 ChemAxon
refractivity 145.05 ChemAxon
polarizability 56.78 ChemAxon
药物相互作用
Drug Interaction
Acenocoumarol Amiodarone may increase the anticoagulant effect of acenocoumarol.
Alvimopan Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Amprenavir The protease inhibitor, amprenavir, may increase the effect and toxicity of amiodarone.
Anisindione Amiodarone may increase the anticoagulant effect of anisindione.
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Atazanavir Increased risk of cardiotoxicity and arrhythmias.
Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clarithromycin Increased risk of cardiotoxicity and arrhythmias
Colesevelam Bile Acid Sequestrants may decrease the bioavailability of Amiodarone. Consider alternative antilipemic agent. The risk of subtherapeutic amiodarone serum concentrations when such is being used for the treatment of malignant arrhythmias can be very large. The effect (ie, reduced risk) of separating doses of these agents is unknown. Amiodarone should be administered at least 1 hour before or 4 hours after colesevelam.1 Similar dosing with other agents seems warranted.
Cyclosporine Amiodarone may increase the therapeutic and adverse effects of cyclosporine.
Dabigatran etexilate Amiodarone may increase the serum concentration of dabigatran etexilate, resulting in increased risk of bleeding. Consider modifying therapy.
Dicumarol Amiodarone may increase the anticoagulant effect of dicumarol.
Digoxin Amiodarone may increase the effect of digoxin.
Dihydroquinidine barbiturate Increases the effect of quinidine
Diltiazem Increased risk of cardiotoxicity and arrhythmias
Eltrombopag Affects hepatic enzyme CYP2C9/10 metabolism, increases effect/level of eltrombopag.
Erythromycin Increased risk of cardiotoxicity and arrhythmias
Ethotoin Increases the effect of hydantoin
Etravirine Amiodarone, when used concomitantly with etravirine, may decrease in serum concentration. If possible, monitoring for decreased amiodarone levels is recommended.
Etravirine Amiodarone, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. If possible, monitoring of amiodarone levels is recommended.
Fentanyl Possible bradycardia, hypotension
Fingolimod Pharmacodynamic synergist. Contraindicated. Increased risk of bradycardia, AV block, and torsade de pointes.
Flecainide Amiodarone may increase the effect and toxicity of flecainide
Fosamprenavir The protease inhibitor, fosamprenavir, may increase the effect and toxicity of amiodarone.
Fosphenytoin Amiodarone may increase the effect of fosphenytoin.
Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Indacaterol Concomitant therapy with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs that prolong the QTc interval should be monitored closely. These drugs may potentiate the effect of adrenergic agonist on the cardiovascular system.
Indinavir Indinavir increases the effect and toxicity of amiodarone
Iohexol Increased risk of cardiotoxicity and arrhythmias
Levofloxacin Increased risk of cardiotoxicity and arrhythmias
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mephenytoin Increases the effect of hydantoin
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Moxifloxacin Increased risk of cardiotoxicity and arrhythmias
Nelfinavir Nelfinavir may increase the effect and toxicity of amiodarone.
Phenytoin Amiodarone may increase the therapeutic and adverse effects of phenytoin.
Procainamide Amiodarone may increase serum levels and toxicity of procainamide.
Quinidine Amiodarone may increase the effect of quinidine.
Quinidine barbiturate Increases the effect of qiunidine
Ranolazine Possible additive effect on QT prolongation
Rifampin Rifampin decreases the effect of amiodarone
Ritonavir Ritonavir increases the effect and toxicity of amiodarone
Roflumilast Increases roflumilast levels.
Saquinavir The protease inhibitor, saquinavir, may increase the effect and toxicity of amiodarone.
Simvastatin Increased risk of rhabdomyolysis
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Tamoxifen Amiodarone may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tamsulosin Amiodarone, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Amiodarone is initiated, discontinued, or dose changed.
Telavancin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Telithromycin Telithromycin may reduce clearance of Amiodarone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Amiodarone if Telithromycin is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Amiodarone. Concomitant therapy is contraindicated.
Tizanidine Amiodarone may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Tolterodine Amiodarone may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
Topotecan The p-glycoprotein inhibitor, Amiodarone, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Tramadol Amiodarone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Amiodarone may decrease the effect of Tramadol by decreasing active metabolite production.
Trazodone The CYP3A4 inhibitor, Amiodarone, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Amiodarone is initiated, discontinued or dose changed.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Vardenafil Increased risk of cardiotoxicity and arrhythmias
Verapamil Additive bradycardic effects may occur. One case report of sinus arrest has been reported. Monitor for changes in the therapeutic effect and signs of Verapamil toxicity if Amiodarone is initiated, discontinued or dose changed.
Voriconazole Additive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of amiodarone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of amiodarone if voriconazole is initiated, discontinued or dose changed.
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Warfarin Amiodarone may increase the anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if amiodarone is initiated, discontinued or dose changed.
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
食物相互作用
  • Grapefruit and grapefruit juice should be avoided throughout treatment.
  • Grapefruit can significantly increase serum levels of this product.
  • Take without regard to meals.

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