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Identification
- Summary
Amiodarone is a class III antiarrhythmic indicated for the treatment of recurrent hemodynamically unstable ventricular tachycardia and recurrent ventricular fibrillation.
- Brand Names
- Nexterone, Pacerone
- Generic Name
- Amiodarone
- DrugBank Accession Number
- DB01118
- Background
Amiodarone is a benzofuran derivative, anti-arrhythmic drug used commonly in a variety of settings.4 Most known for its approved indication in life-threatening ventricular arrhythmias, it is also used off-label in the outpatient and inpatient setting for atrial fibrillation. Because of its ability to cause serious toxicity and possibly death, amiodarone use should be reserved for its approved indications, according to prescribing information.18,19,20
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Amiodarone (DB01118)
- Weight
- Average: 645.3116
Monoisotopic: 645.023680639 - Chemical Formula
- C25H29I2NO3
- Synonyms
- 2-Butyl-3-(3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl)benzofuran
- 2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone
- 2-n-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuran
- Amiodarona
- Amiodarone
- Amiodaronum
Pharmacology
- Indication
The FDA approved indications for amiodarone are recurrent ventricular fibrillation (VF) and recurrent hemodynamically unstable ventricular tachycardia (VT). The FDA emphasizes that this drug should only be given in these conditions when they are clinically documented and have not responded to normal therapeutic doses of other antiarrhythmic agents, or when other drugs are not tolerated by the patient.18
Off-label indications include atrial fibrillation and supraventricular tachycardia.7,8,9,20
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Atrial fibrillation ••• ••••• Prevention of Atrial fibrillation ••• ••••• Management of Supraventricular tachycardia ••• ••••• Management of Recurrent ventricular fibrillation •••••••••••• Management of Recurrent hemodynamically unstable ventricular tachycardia •••••••••••• - Contraindications & Blackbox Warnings
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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.2,7,18 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.18
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.19 Thyrotoxicosis or hypothyroidism may also result from the administration of amiodarone, which contains high levels of iodine, and interferes with normal thyroid function.11
- Mechanism of action
Amiodarone is considered a class III anti-arrhythmic drug. It blocks potassium currents that cause repolarization of the heart muscle during the third phase of the cardiac action potential. As a result amiodarone increases the duration of the action potential as well as the effective refractory period for cardiac cells (myocytes). Therefore, cardiac muscle cell excitability is reduced, preventing and treating abnormal heart rhythms.5,10
Unique from other members of the class III anti-arrhythmic drug class, amiodarone also interferes with the functioning of beta-adrenergic receptors, sodium channels, and calcium channels channels. These actions, at times, can lead to undesirable effects, such as hypotension, bradycardia, and Torsades de pointes (TdP).19 In addition to the above, amiodarone may increase activity of peroxisome proliferator-activated receptors, leading to steatogenic changes in the liver or other organs.14,15 Finally, amiodarone has been found to bind to the thyroid receptor due to its iodine content, potentially leading to amiodarone induced hypothyroidism or thyrotoxicosis.11
Target Actions Organism AHERG human cardiac K+ channel inhibitorHumans ABeta adrenergic receptor inhibitordownregulatorHumans UVoltage-dependent T-type calcium channel subunit alpha-1I inhibitorHumans UVoltage gated L-type calcium channel inhibitorHumans UThyroid hormone receptor antagonistbinderHumans and other mammals UPeroxisome proliferator-activated receptor gamma agonistHumans UPeroxisome proliferator-activated receptor alpha agonistHumans UPeroxisome proliferator-activated receptor gamma coactivator 1-beta agonistHumans - Absorption
The Cmax of amiodarone in the plasma is achieved about 3 to 7 hours after administration.18 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.4,5
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.18 The bioavailability of amiodarone varies in clinical studies, averaging between 35 and 65%.18
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.18 Food also enhances absorption, reducing the Tmax by about 37%.18
- Volume of distribution
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.6 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 tissue4 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.18
- Protein binding
- Metabolism
This drug is metabolized to the main metabolite desethylamiodarone (DEA)4 by the CYP3A4 and CYP2C8 enzymes. The CYP3A4 enzyme is found in the liver and intestines.18 A hydroxyl metabolite of DEA has been identified in mammals, but its clinical significance is unknown.12
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- Route of elimination
Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion.4 A small amount of desethylamiodarone (DEA) is found in the urine.18
- 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. 3,7 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).18 The plasma half-life of amiodarone after one dose ranges from 3.2 to 79.7 hours, according to one source.4
- Clearance
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.18 Another study determined that the total body clearance of amiodarone varies from 0.10 to 0.77 L/min after one intravenous dose.4 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.18
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.18
- Adverse Effects
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The LD50 of oral amiodarone in mice and rats exceeds 3,000 mg/kg.18 An overdose with amiodarone can have a fatal outcome due to its potential to cause arrhythmia. Signs or symptoms of an overdose may include, hypotension, shock, bradycardia, AV block, and liver toxicity. In cases of an overdose, initiate supportive treatment and, if needed, use fluids, vasopressors, or positive inotropic agents. Temporary pacing may be required for heart block. Ensure to monitor liver function regularly. Amiodarone and its main metabolite, DEA, are not removable by dialysis.17
- Pathways
Pathway Category Amiodarone Action Pathway Drug action - Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Potassium voltage-gated channel subfamily H member 2 MiRP1 Not Available KCNE2 ADR Directly Studied The presence of polymorphisms in KCNH2 and KCNE2 may potentially be associated with increased susceptibility to long Q-T syndrome or cardiac arrhytmia when treated with amiodarone. Details
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Amiodarone. Abaloparatide The risk or severity of adverse effects can be increased when Amiodarone is combined with Abaloparatide. Abametapir The serum concentration of Amiodarone can be increased when it is combined with Abametapir. Abatacept The metabolism of Amiodarone can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Amiodarone. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of amiodarone.
- Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of amiodarone. Therefore it may reduce the serum concentration and effectiveness of amiodarone.
- Take with or without food. The absorption is unaffected by food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Amiodarone hydrochloride 976728SY6Z 19774-82-4 ITPDYQOUSLNIHG-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Amio-Aqueous IV / Aratac / Arycor / Atlansil / Tachyra
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Amiodarone Tablet 200 mg Oral Sanis Health Inc 2011-06-10 Not applicable Canada 
Amiodarone Tablet 200 mg Oral Sorres Pharma Inc 2009-06-23 2014-06-20 Canada Amiodarone Tablet 200 mg Oral Sivem Pharmaceuticals Ulc 2012-06-10 Not applicable Canada Amiodarone for Injection 50mg/ml Solution 50 mg / mL Intravenous TEVA Canada Limited 2004-04-21 2018-02-23 Canada Amiodarone HCl Injection, solution 1.8 mg/1mL Intravenous Cantrell Drug Company 2013-10-18 Not applicable US 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Amiodarone Hci Injection, solution 50 mg/1mL Intravenous HF Acquisition Co LLC, DBA HealthFirst 2019-12-08 Not applicable US Amiodarone HCl Tablet 100 mg/1 Oral Cameron Pharmaceuticals, LLC 2017-01-01 Not applicable US Amiodarone HCl Tablet 200 mg/1 Oral Mayne Pharma Inc. 2013-01-01 2019-12-31 US Amiodarone HCl Tablet 100 mg/1 Oral bryant ranch prepack 2017-01-01 Not applicable US Amiodarone HCl Tablet 400 mg/1 Oral Cameron Pharmaceuticals, LLC 2013-01-01 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Amiodarone HCl Amiodarone hydrochloride (1.8 mg/1mL) Injection, solution Intravenous Cantrell Drug Company 2013-10-18 Not applicable US
Categories
- ATC Codes
- C01BD01 — Amiodarone
- Drug Categories
- Agents causing hyperkalemia
- Agents Causing Muscle Toxicity
- alpha-Galactosidase, antagonists & inhibitors
- Antiarrhythmic agents
- Antiarrhythmics, Class III
- Benzofurans
- Bradycardia-Causing Agents
- BSEP/ABCB11 Inhibitors
- BSEP/ABCB11 Substrates
- BSEP/ABCB11 Substrates with a Narrow Therapeutic Index
- Calcium Channel Blockers
- Cardiac Therapy
- Cardiovascular Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strong)
- Cytochrome P-450 CYP2A6 Inhibitors
- Cytochrome P-450 CYP2A6 Inhibitors (moderate)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors (strong)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs causing inadvertant photosensitivity
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Highest Risk QTc-Prolonging Agents
- Hypotensive Agents
- Membrane Transport Modulators
- Narrow Therapeutic Index Drugs
- OCT2 Inhibitors
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- Photosensitizing Agents
- Potassium Channel Blockers
- QTc Prolonging Agents
- Sodium Channel Blockers
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbonyl compounds
- Direct Parent
- Aryl-phenylketones
- Alternative Parents
- Benzofurans / Phenoxy compounds / Phenol ethers / Benzoyl derivatives / 3-aroylfurans / Iodobenzenes / Alkyl aryl ethers / Aryl iodides / Heteroaromatic compounds / Trialkylamines show 5 more
- Substituents
- 3-aroylfuran / Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Aryl halide / Aryl iodide / Aryl-phenylketone / Benzenoid / Benzofuran / Benzoyl show 19 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tertiary amino compound, organoiodine compound, 1-benzofurans, aromatic ketone (CHEBI:2663)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- N3RQ532IUT
- CAS number
- 1951-25-3
- InChI Key
- IYIKLHRQXLHMJQ-UHFFFAOYSA-N
- InChI
- 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
- IUPAC Name
- {2-[4-(2-butyl-1-benzofuran-3-carbonyl)-2,6-diiodophenoxy]ethyl}diethylamine
- SMILES
- CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=C(O1)C=CC=C2
References
- Synthesis Reference
M.J.A. Walker, P.P.S. Therapeutic Areas I: Central Nervous System, Pain, Metabolic Syndrome, Urology, Gastrointestinal and Cardiovascular: Amiodarone. Comprehensive Medicinal Chemistry II, 2007
US3248401- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Latini R, Tognoni G, Kates RE: Clinical pharmacokinetics of amiodarone. Clin Pharmacokinet. 1984 Mar-Apr;9(2):136-56. doi: 10.2165/00003088-198409020-00002. [Article]
- Zipes DP, Prystowsky EN, Heger JJ: Amiodarone: electrophysiologic actions, pharmacokinetics and clinical effects. J Am Coll Cardiol. 1984 Apr;3(4):1059-71. doi: 10.1016/s0735-1097(84)80367-8. [Article]
- Riva E, Gerna M, Latini R, Giani P, Volpi A, Maggioni A: Pharmacokinetics of amiodarone in man. J Cardiovasc Pharmacol. 1982 Mar-Apr;4(2):264-9. doi: 10.1097/00005344-198203000-00015. [Article]
- Freedman MD, Somberg JC: Pharmacology and pharmacokinetics of amiodarone. J Clin Pharmacol. 1991 Nov;31(11):1061-9. doi: 10.1002/j.1552-4604.1991.tb03673.x. [Article]
- Rowland E, Krikler DM: Electrophysiological assessment of amiodarone in treatment of resistant supraventricular arrhythmias. Br Heart J. 1980 Jul;44(1):82-90. doi: 10.1136/hrt.44.1.82. [Article]
- Soult JA, Munoz M, Lopez JD, Romero A, Santos J, Tovaruela A: Efficacy and safety of intravenous amiodarone for short-term treatment of paroxysmal supraventricular tachycardia in children. Pediatr Cardiol. 1995 Jan-Feb;16(1):16-9. doi: 10.1007/BF02310328. [Article]
- Honjo H, Kodama I, Kamiya K, Toyama J: Block of cardiac sodium channels by amiodarone studied by using Vmax of action potential in single ventricular myocytes. Br J Pharmacol. 1991 Mar;102(3):651-6. doi: 10.1111/j.1476-5381.1991.tb12228.x. [Article]
- Narayana SK, Woods DR, Boos CJ: Management of amiodarone-related thyroid problems. Ther Adv Endocrinol Metab. 2011 Jun;2(3):115-26. doi: 10.1177/2042018811398516. [Article]
- Ha HR, Bigler L, Binder M, Kozlik P, Stieger B, Hesse M, Altorfer HR, Follath F: Metabolism of amiodarone (part I): identification of a new hydroxylated metabolite of amiodarone. Drug Metab Dispos. 2001 Feb;29(2):152-8. [Article]
- Deng P, You T, Chen X, Yuan T, Huang H, Zhong D: Identification of amiodarone metabolites in human bile by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. Drug Metab Dispos. 2011 Jun;39(6):1058-69. doi: 10.1124/dmd.110.037671. Epub 2011 Mar 11. [Article]
- Szalowska E, van der Burg B, Man HY, Hendriksen PJ, Peijnenburg AA: Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices. PLoS One. 2014 Jan 29;9(1):e86795. doi: 10.1371/journal.pone.0086795. eCollection 2014. [Article]
- Song M, Kim YJ, Ryu JC: Phospholipidosis induced by PPARgamma signaling in human bronchial epithelial (BEAS-2B) cells exposed to amiodarone. Toxicol Sci. 2011 Mar;120(1):98-108. doi: 10.1093/toxsci/kfq361. Epub 2010 Dec 1. [Article]
- Electronic Medicines Compendium Amiodarone 100mg Tablets [Link]
- Nexterone FDA label [Link]
- FDA Approved Drug Products: CORDARONE (amiodarone HCl) tablets [Link]
- NIH StatPearls: Amiodarone [Link]
- AAFP: Medication Guide for Amiodarone [Link]
- FDA Approved Drug Products: NEXTERONE (amiodarone HCl) injection [Link]
- External Links
- Human Metabolome Database
- HMDB0015250
- KEGG Drug
- D02910
- KEGG Compound
- C06823
- PubChem Compound
- 2157
- PubChem Substance
- 46507387
- ChemSpider
- 2072
- BindingDB
- 18957
- 703
- ChEBI
- 2663
- ChEMBL
- CHEMBL633
- ZINC
- ZINC000003830212
- Therapeutic Targets Database
- DAP000496
- PharmGKB
- PA448383
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- BBI
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Amiodarone
- PDB Entries
- 4o8z / 5h4d / 8e56 / 8e57 / 8e58 / 8e59 / 8e5b / 8fhs
- MSDS
- Download (51.8 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Arrhythmia 1 somestatus stop reason just information to hide Not Available Completed Not Available Atrial Fibrillation / Tachycardia Atrial 1 somestatus stop reason just information to hide Not Available Completed Not Available Cardiac Arrest / Sudden Cardiac Death 1 somestatus stop reason just information to hide Not Available Completed Not Available Out-of-hospital Cardiac Arrest (OHCA) 1 somestatus stop reason just information to hide Not Available Completed Prevention Atrial Fibrillation 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Alphapharm Party Ltd.
- Amerisource Health Services Corp.
- Amphastar Pharmaceuticals
- Apotex Inc.
- APP Pharmaceuticals
- A-S Medication Solutions LLC
- Aurolife Pharma LLC
- Aurosal Pharmaceuticals LLC
- Barr Pharmaceuticals
- Baxter International Inc.
- Bedford Labs
- Ben Venue Laboratories Inc.
- Bioniche Pharma
- Cadila Healthcare Ltd.
- Cardinal Health
- Caremark LLC
- Diversified Healthcare Services Inc.
- Eon Labs
- General Injectables and Vaccines Inc.
- Gland Pharma Ltd.
- Heartland Repack Services LLC
- Hikma Pharmaceuticals
- Hospira Inc.
- Mckesson Corp.
- Murfreesboro Pharmaceutical Nursing Supply
- Murty Pharmaceuticals Inc.
- Mylan
- Neuman Distributors Inc.
- Novex Pharma
- Novopharm Ltd.
- Par Pharmaceuticals
- Physicians Total Care Inc.
- Prepak Systems Inc.
- Remedy Repack
- Resource Optimization and Innovation LLC
- Sagent Pharmaceuticals
- Sandhills Packaging Inc.
- Sandoz
- Sanofi-Aventis Inc.
- Sicor Pharmaceuticals
- Spectrum Pharmaceuticals
- Taro Pharmaceuticals USA
- Teva Pharmaceutical Industries Ltd.
- UDL Laboratories
- Upsher Smith Laboratories
- Vangard Labs Inc.
- West-Ward Pharmaceuticals
- Wockhardt Ltd.
- Wyeth Pharmaceuticals
- Zydus Pharmaceuticals
- Dosage Forms
Form Route Strength Capsule 200 MG Injection, solution Parenteral Solution Parenteral 50 mg Injection Parenteral 150 mg Solution Parenteral 150 mg Injection, solution Parenteral 150 MG/3ML Injection, solution Injection, solution 20 MG/ML Injection 50 mg/mL Injection, solution Intravenous 1.8 mg/1mL Injection, solution, concentrate Intravenous 150 mg/3mL Injection, solution Parenteral 50 MG/ML Injection Intravenous 150 mg/3mL Injection Intravenous 450 mg/9mL Injection Intravenous 50 mg/1mL Injection Intravenous 900 mg/18mL Injection, solution Intravenous 150 mg/3mL Injection, solution Intravenous 450 mg/9mL Injection, solution Intravenous 50 mg/1mL Injection, solution Intravenous 900 mg/18mL Tablet Oral 200 mg/1 Tablet Oral 300 mg/1 Solution Intravenous 50 mg / mL Injection, solution Intravenous Injection Intramuscular 150 mg Tablet Oral 200.0000 mg Tablet Oral 200 mg Solution Parenteral 150.000 mg Tablet Oral 200.000 mg Solution Intravenous 150 mg/3ml Tablet Oral Liquid Intravenous 50 mg / mL Solution Intravenous 150 mg Injection Intravenous Solution Intravenous 150.000 mg Injection, solution, concentrate Intravenous 50 mg/mL Injection Intravenous 50 mg/ml Injection Parenteral Injection, solution Intravenous 1.5 mg/1mL Tablet Oral 100 mg/1 Tablet Oral 400 mg/1 Tablet Oral 100 mg Solution 50 mg/1ml - Prices
Unit description Cost Unit Amiodarone hcl powder 38.98USD g Pacerone 100 mg tablet 7.58USD tablet Pacerone 400 mg tablet 7.43USD tablet Amiodarone hcl 400 mg tablet 6.32USD tablet Cordarone 200 mg tablet 4.78USD tablet Pacerone 200 mg tablet 3.53USD tablet Amiodarone hcl 200 mg tablet 3.37USD tablet Cordarone 200 mg Tablet 2.32USD tablet Apo-Amiodarone 200 mg Tablet 1.3USD tablet Mylan-Amiodarone 200 mg Tablet 1.3USD tablet Novo-Amiodarone 200 mg Tablet 1.3USD tablet Pms-Amiodarone 200 mg Tablet 1.3USD tablet Ratio-Amiodarone 200 mg Tablet 1.3USD tablet Sandoz Amiodarone 200 mg Tablet 1.3USD tablet Amiodarone 150 mg/3 ml vial 0.83USD ml Pms-Amiodarone 100 mg Tablet 0.72USD tablet Amiodarone 900 mg/18 ml vial 0.59USD ml Amiodarone 450 mg/9 ml vial 0.57USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5134127 No 1992-07-28 2010-01-23 US US6869939 No 2005-03-22 2022-05-04 US US7635773 No 2009-12-22 2029-03-13 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 156 O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 85. Marly, SA, Belgium. boiling point (°C) 100 https://auromedics.com/wordpress/wp-content/uploads/Amiodarone-Hydrochloride-Injection-USP-SDS-US-11-28-17.pdf water solubility Low https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018972s042lbl.pdf logP 7.2 https://journals.lww.com/md-journal/fulltext/2018/09140/comedication_with_interacting_drugs_predisposes.46.aspx pKa 6.56 ± 0.06 https://www.chemicalbook.com/ChemicalProductProperty_US_CB7131332.aspx - Predicted Properties
Property Value Source Water Solubility 0.00476 mg/mL 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 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 145.05 m3·mol-1 Chemaxon Polarizability 56.78 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.8615 Caco-2 permeable + 0.66 P-glycoprotein substrate Substrate 0.8044 P-glycoprotein inhibitor I Inhibitor 0.8563 P-glycoprotein inhibitor II Inhibitor 0.8388 Renal organic cation transporter Inhibitor 0.5099 CYP450 2C9 substrate Non-substrate 0.7959 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.7188 CYP450 1A2 substrate Inhibitor 0.9106 CYP450 2C9 inhibitor Inhibitor 0.8948 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8615 Ames test Non AMES toxic 0.5661 Carcinogenicity Non-carcinogens 0.7696 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6539 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.5932 hERG inhibition (predictor II) Inhibitor 0.7638
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 219.0648071 predictedDarkChem Lite v0.1.0 [M-H]- 223.23326 predictedDeepCCS 1.0 (2019) [M+H]+ 220.3645071 predictedDarkChem Lite v0.1.0 [M+H]+ 225.59126 predictedDeepCCS 1.0 (2019) [M+Na]+ 219.2856071 predictedDarkChem Lite v0.1.0 [M+Na]+ 233.272 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (PubMed:18559421, PubMed:26363003, PubMed:27916661)
- Specific Function
- C3hc4-type ring finger domain binding
Components:
| Name | UniProt ID |
|---|---|
| Potassium voltage-gated channel subfamily H member 2 | Q12809 |
| Potassium voltage-gated channel subfamily H member 6 | Q9H252 |
| Potassium voltage-gated channel subfamily H member 7 | Q9NS40 |
References
- Wang SP, Wang JA, Luo RH, Cui WY, Wang H: Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation. Clin Exp Pharmacol Physiol. 2008 Sep;35(9):1077-84. doi: 10.1111/j.1440-1681.2008.04964.x. Epub 2008 May 25. [Article]
- Varro A, Biliczki P, Iost N, Virag L, Hala O, Kovacs P, Matyus P, Papp JG: Theoretical possibilities for the development of novel antiarrhythmic drugs. Curr Med Chem. 2004 Jan;11(1):1-11. [Article]
- Waldhauser KM, Brecht K, Hebeisen S, Ha HR, Konrad D, Bur D, Krahenbuhl S: Interaction with the hERG channel and cytotoxicity of amiodarone and amiodarone analogues. Br J Pharmacol. 2008 Oct;155(4):585-95. doi: 10.1038/bjp.2008.287. Epub 2008 Jul 7. [Article]
- FDA Approved Drug Products: CORDARONE (amiodarone HCl) tablets [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InhibitorDownregulator
- General Function
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. Involved in the regulation of sleep/wake behaviors (PubMed:31473062)
- Specific Function
- Alpha-2a adrenergic receptor binding
Components:
| Name | UniProt ID |
|---|---|
| Beta-1 adrenergic receptor | P08588 |
| Beta-2 adrenergic receptor | P07550 |
| Beta-3 adrenergic receptor | P13945 |
References
- Drvota V, Haggblad J, Blange I, Magnusson Y, Sylven S: The effect of amiodarone on the beta-adrenergic receptor is due to a downregulation of receptor protein and not to a receptor-ligand interaction. Biochem Biophys Res Commun. 1999 Feb 16;255(2):515-20. doi: 10.1006/bbrc.1998.0138. [Article]
- Disatnik MH, Shainberg A: Regulation of beta-adrenoceptors by thyroid hormone and amiodarone in rat myocardiac cells in culture. Biochem Pharmacol. 1991 Mar 15-Apr 1;41(6-7):1039-44. doi: 10.1016/0006-2952(91)90212-n. [Article]
- FDA Approved Drug Products: CORDARONE (amiodarone HCl) tablets [Link]
- NIH StatPearls: Amiodarone [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This channel gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H (By similarity)
- Specific Function
- High voltage-gated calcium channel activity
- Gene Name
- CACNA1I
- Uniprot ID
- Q9P0X4
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1I
- Molecular Weight
- 245100.8 Da
References
- Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [Article]
- Lewalter T, Pittrow D, Goette A, Kirch W, Hohnloser S: [Clinical pharmacology and electrophysiological properties of dronedarone]. Dtsch Med Wochenschr. 2010 Mar;135 Suppl 2:S43-7. doi: 10.1055/s-0030-1249208. Epub 2010 Mar 10. [Article]
- Lubic SP, Nguyen KP, Dave B, Giacomini JC: Antiarrhythmic agent amiodarone possesses calcium channel blocker properties. J Cardiovasc Pharmacol. 1994 Nov;24(5):707-14. doi: 10.1097/00005344-199424050-00004. [Article]
- NIH StatPearls: Amiodarone [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:11741969, PubMed:12176756, PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17071743, PubMed:17224476, PubMed:20953164, PubMed:23677916, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:29078335, PubMed:29742403, PubMed:30023270, PubMed:30172029, PubMed:34163037, PubMed:7737988, PubMed:8099908, PubMed:8392192, PubMed:9013606, PubMed:9087614, PubMed:9607315). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable)
- Specific Function
- Alpha-actinin binding
Components:
References
- Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [Article]
- Lewalter T, Pittrow D, Goette A, Kirch W, Hohnloser S: [Clinical pharmacology and electrophysiological properties of dronedarone]. Dtsch Med Wochenschr. 2010 Mar;135 Suppl 2:S43-7. doi: 10.1055/s-0030-1249208. Epub 2010 Mar 10. [Article]
- Lubic SP, Nguyen KP, Dave B, Giacomini JC: Antiarrhythmic agent amiodarone possesses calcium channel blocker properties. J Cardiovasc Pharmacol. 1994 Nov;24(5):707-14. doi: 10.1097/00005344-199424050-00004. [Article]
- Watanabe Y, Kimura J: Inhibitory effect of amiodarone on Na(+)/Ca(2+) exchange current in guinea-pig cardiac myocytes. Br J Pharmacol. 2000 Sep;131(1):80-4. doi: 10.1038/sj.bjp.0703527. [Article]
- NIH StatPearls: Amiodarone [Link]
- Kind
- Protein group
- Organism
- Humans and other mammals
- Pharmacological action
- Unknown
- Actions
- AntagonistBinder
- General Function
- Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine
- Specific Function
- Chromatin dna binding
Components:
References
- Carlsson B, Singh BN, Temciuc M, Nilsson S, Li YL, Mellin C, Malm J: Synthesis and preliminary characterization of a novel antiarrhythmic compound (KB130015) with an improved toxicity profile compared with amiodarone. J Med Chem. 2002 Jan 31;45(3):623-30. [Article]
- Norman MF, Lavin TN: Antagonism of thyroid hormone action by amiodarone in rat pituitary tumor cells. J Clin Invest. 1989 Jan;83(1):306-13. doi: 10.1172/JCI113874. [Article]
- Narayana SK, Woods DR, Boos CJ: Management of amiodarone-related thyroid problems. Ther Adv Endocrinol Metab. 2011 Jun;2(3):115-26. doi: 10.1177/2042018811398516. [Article]
- NIH StatPearls: Amiodarone [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity)
- Specific Function
- Alpha-actinin binding
- Gene Name
- PPARG
- Uniprot ID
- P37231
- Uniprot Name
- Peroxisome proliferator-activated receptor gamma
- Molecular Weight
- 57619.58 Da
References
- Szalowska E, van der Burg B, Man HY, Hendriksen PJ, Peijnenburg AA: Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices. PLoS One. 2014 Jan 29;9(1):e86795. doi: 10.1371/journal.pone.0086795. eCollection 2014. [Article]
- Song M, Kim YJ, Ryu JC: Phospholipidosis induced by PPARgamma signaling in human bronchial epithelial (BEAS-2B) cells exposed to amiodarone. Toxicol Sci. 2011 Mar;120(1):98-108. doi: 10.1093/toxsci/kfq361. Epub 2010 Dec 1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as a transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2
- Specific Function
- Dna binding
- Gene Name
- PPARA
- Uniprot ID
- Q07869
- Uniprot Name
- Peroxisome proliferator-activated receptor alpha
- Molecular Weight
- 52224.595 Da
References
- Szalowska E, van der Burg B, Man HY, Hendriksen PJ, Peijnenburg AA: Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices. PLoS One. 2014 Jan 29;9(1):e86795. doi: 10.1371/journal.pone.0086795. eCollection 2014. [Article]
- McCarthy TC, Pollak PT, Hanniman EA, Sinal CJ: Disruption of hepatic lipid homeostasis in mice after amiodarone treatment is associated with peroxisome proliferator-activated receptor-alpha target gene activation. J Pharmacol Exp Ther. 2004 Dec;311(3):864-73. doi: 10.1124/jpet.104.072785. Epub 2004 Jul 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Plays a role of stimulator of transcription factors and nuclear receptors activities. Activates transcriptional activity of estrogen receptor alpha, nuclear respiratory factor 1 (NRF1) and glucocorticoid receptor in the presence of glucocorticoids. May play a role in constitutive non-adrenergic-mediated mitochondrial biogenesis as suggested by increased basal oxygen consumption and mitochondrial number when overexpressed. May be involved in fat oxidation and non-oxidative glucose metabolism and in the regulation of energy expenditure. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner
- Specific Function
- Af-2 domain binding
- Gene Name
- PPARGC1B
- Uniprot ID
- Q86YN6
- Uniprot Name
- Peroxisome proliferator-activated receptor gamma coactivator 1-beta
- Molecular Weight
- 113221.09 Da
References
- Szalowska E, van der Burg B, Man HY, Hendriksen PJ, Peijnenburg AA: Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices. PLoS One. 2014 Jan 29;9(1):e86795. doi: 10.1371/journal.pone.0086795. eCollection 2014. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- Curator comments
- Amiodarone competitively inhibits the CYP3A4 as it is a substrate of this enzyme.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Elsherbiny ME, El-Kadi AO, Brocks DR: The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci. 2008;11(1):147-59. [Article]
- Ohyama K, Nakajima M, Nakamura S, Shimada N, Yamazaki H, Yokoi T: A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab Dispos. 2000 Nov;28(11):1303-10. [Article]
- Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br J Clin Pharmacol. 2000 Mar;49(3):244-53. doi: 10.1046/j.1365-2125.2000.00134.x. [Article]
- Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L53). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Electronic Medicines Compendium Amiodarone 100mg Tablets [Link]
- FDA Approved Drug Products: CORDARONE (amiodarone HCl) tablets [Link]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- Arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Ohyama K, Nakajima M, Nakamura S, Shimada N, Yamazaki H, Yokoi T: A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab Dispos. 2000 Nov;28(11):1303-10. [Article]
- Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L53). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
- FDA Approved Drug Products: CORDARONE (amiodarone HCl) tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Yamreudeewong W, DeBisschop M, Martin LG, Lower DL: Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Saf. 2003;26(6):421-38. doi: 10.2165/00002018-200326060-00004. [Article]
- Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br J Clin Pharmacol. 2000 Mar;49(3):244-53. doi: 10.1046/j.1365-2125.2000.00134.x. [Article]
- Fukumoto K, Kobayashi T, Tachibana K, Kato R, Tanaka K, Komamura K, Kamakura S, Kitakaze M, Ueno K: Effect of amiodarone on the serum concentration/dose ratio of metoprolol in patients with cardiac arrhythmia. Drug Metab Pharmacokinet. 2006 Dec;21(6):501-5. [Article]
- Jaruratanasirikul S, Hortiwakul R: The inhibitory effect of amiodarone and desethylamiodarone on dextromethorphan O-demethylation in human and rat liver microsomes. J Pharm Pharmacol. 1994 Nov;46(11):933-5. doi: 10.1111/j.2042-7158.1994.tb05721.x. [Article]
- Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L53). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Flockhart Table of Drug Interactions [Link]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Yamreudeewong W, DeBisschop M, Martin LG, Lower DL: Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Saf. 2003;26(6):421-38. doi: 10.2165/00002018-200326060-00004. [Article]
- Naganuma M, Shiga T, Nishikata K, Tsuchiya T, Kasanuki H, Fujii E: Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy. J Cardiovasc Pharmacol Ther. 2001 Oct;6(4):363-7. doi: 10.1177/107424840100600405. [Article]
- Heimark LD, Wienkers L, Kunze K, Gibaldi M, Eddy AC, Trager WF, O'Reilly RA, Goulart DA: The mechanism of the interaction between amiodarone and warfarin in humans. Clin Pharmacol Ther. 1992 Apr;51(4):398-407. [Article]
- Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L53). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Drug Interactions & Labeling - FDA [Link]
- Flockhart Table of Drug Interactions [Link]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- The induction of p-gp by glycoprotein is only supported by data from in vitro studies. Clinical relevance is unknown.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- Aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- Naganuma M, Shiga T, Nishikata K, Tsuchiya T, Kasanuki H, Fujii E: Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy. J Cardiovasc Pharmacol Ther. 2001 Oct;6(4):363-7. doi: 10.1177/107424840100600405. [Article]
- McDonald MG, Au NT, Rettie AE: P450-Based Drug-Drug Interactions of Amiodarone and its Metabolites: Diversity of Inhibitory Mechanisms. Drug Metab Dispos. 2015 Nov;43(11):1661-9. doi: 10.1124/dmd.115.065623. Epub 2015 Aug 21. [Article]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Flockhart Table of Drug Interactions [Link]
- FDA Approved Drug Products: CORDARONE (amiodarone HCl) tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- CYP2C19 plays a minor role in amiodarone metabolism and is unlikely to cause clinically significant interaction.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Ohyama K, Nakajima M, Nakamura S, Shimada N, Yamazaki H, Yokoi T: A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab Dispos. 2000 Nov;28(11):1303-10. [Article]
- Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br J Clin Pharmacol. 2000 Mar;49(3):244-53. doi: 10.1046/j.1365-2125.2000.00134.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
- Specific Function
- Arachidonic acid monooxygenase activity
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Elsherbiny ME, El-Kadi AO, Brocks DR: The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci. 2008;11(1):147-59. [Article]
- Wu Q, Ning B, Xuan J, Ren Z, Guo L, Bryant MS: The role of CYP 3A4 and 1A1 in amiodarone-induced hepatocellular toxicity. Toxicol Lett. 2016 Jun 24;253:55-62. doi: 10.1016/j.toxlet.2016.04.016. Epub 2016 Apr 22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Data regarding this enzyme action are limited in the literature.
- General Function
- Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity
- Specific Function
- Arachidonic acid epoxygenase activity
- Gene Name
- CYP2A6
- Uniprot ID
- P11509
- Uniprot Name
- Cytochrome P450 2A6
- Molecular Weight
- 56517.005 Da
References
- Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br J Clin Pharmacol. 2000 Mar;49(3):244-53. doi: 10.1046/j.1365-2125.2000.00134.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) in the cardiovascular system (PubMed:19965576, PubMed:8631948). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:19965576, PubMed:8631948). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:8631948). Converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE), likely playing a major role in the epoxidation of endogenous cardiac arachidonic acid pools (PubMed:8631948). In endothelial cells, participates in eicosanoids metabolism by converting hydroperoxide species into hydroxy epoxy metabolites. In combination with 15-lipoxygenase metabolizes arachidonic acid and converts hydroperoxyicosatetraenoates (HpETEs) into hydroxy epoxy eicosatrienoates (HEETs), which are precursors of vasodilatory trihydroxyicosatrienoic acids (THETAs). This hydroperoxide isomerase activity is NADPH- and O2-independent (PubMed:19737933). Catalyzes the monooxygenation of a various xenobiotics, such as danazol, amiodarone, terfenadine, astemizole, thioridazine, tamoxifen, cyclosporin A and nabumetone (PubMed:19923256). Catalyzes hydroxylation of the anthelmintics albendazole and fenbendazole (PubMed:23959307). Catalyzes the sulfoxidation of fenbedazole (PubMed:19923256)
- Specific Function
- Arachidonic acid 11,12-epoxygenase activity
- Gene Name
- CYP2J2
- Uniprot ID
- P51589
- Uniprot Name
- Cytochrome P450 2J2
- Molecular Weight
- 57610.165 Da
References
- Karkhanis A, Lam HY, Venkatesan G, Koh SK, Chai CL, Zhou L, Hong Y, Kojodjojo P, Chan EC: Multiple modes of inhibition of human cytochrome P450 2J2 by dronedarone, amiodarone and their active metabolites. Biochem Pharmacol. 2016 May 1;107:67-80. doi: 10.1016/j.bcp.2016.03.005. Epub 2016 Mar 10. [Article]
- Karkhanis A, Tram NDT, Chan ECY: Effects of dronedarone, amiodarone and their active metabolites on sequential metabolism of arachidonic acid to epoxyeicosatrienoic and dihydroxyeicosatrienoic acids. Biochem Pharmacol. 2017 Dec 15;146:188-198. doi: 10.1016/j.bcp.2017.09.012. Epub 2017 Sep 25. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- Antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Veronese ME, McLean S, Hendriks R: Plasma protein binding of amiodarone in a patient population: measurement by erythrocyte partitioning and a novel glass-binding method. Br J Clin Pharmacol. 1988 Dec;26(6):721-31. doi: 10.1111/j.1365-2125.1988.tb05311.x. [Article]
- Neyroz P, Bonati M: In vitro amiodarone protein binding and its interaction with warfarin. Experientia. 1985 Mar 15;41(3):361-3. doi: 10.1007/bf02004505. [Article]
- Lalloz MR, Byfield PG, Greenwood RM, Himsworth RL: Binding of amiodarone by serum proteins and the effects of drugs, hormones and other interacting ligands. J Pharm Pharmacol. 1984 Jun;36(6):366-72. doi: 10.1111/j.2042-7158.1984.tb04400.x. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- Curator comments
- The induction of p-glycoprotein by amiodarone is only supported by in vitro data. Clinical relevance is unknown.
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Schuetz EG, Beck WT, Schuetz JD: Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol. 1996 Feb;49(2):311-8. [Article]
- Katoh M, Nakajima M, Yamazaki H, Yokoi T: Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport. Eur J Pharm Sci. 2001 Feb;12(4):505-13. [Article]
- Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. [Article]
- Tiberghien F, Loor F: Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anticancer Drugs. 1996 Jul;7(5):568-78. [Article]
- Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR: Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999 Mar;16(3):408-14. [Article]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- Curator comments
- There are limited data in the literature to support this transporter action. It is not likely to be clinically significant.
- General Function
- Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
- Specific Function
- Abc-type bile acid transporter activity
- Gene Name
- ABCB11
- Uniprot ID
- O95342
- Uniprot Name
- Bile salt export pump
- Molecular Weight
- 146405.83 Da
References
- Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- Acetylcholine transmembrane transporter activity
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
Drug created at June 13, 2005 13:24 / Updated at September 15, 2024 21:55