Banner
Identification
Name Amiodarone
Accession Number DB01118 (APRD00288)
Type small molecule
Groups approved
Description

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]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Amiodarona [INN-Spanish]
Amiodarone Base
Amiodarone HCL
Amiodarone Hydrochloride
Amiodaronum [INN-Latin]
Salts Not Available
Brand names
Name Company
Aminodarone
Amio-Aqueous IV
Amiodarons
Aratac
Arycor
Cordarone
Cordarone Intravenous
Labaz
Pacerone
pms-Amiodarone
Brand mixtures Not Available
Categories
  • Vasodilator Agents
  • Enzyme Inhibitors
  • Anti-Arrhythmia Agents
CAS number 1951-25-3
Weight Average: 645.3116
Monoisotopic: 645.023680639
Chemical Formula C25H29I2NO3
InChI Key InChIKey=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
Plain Text
IUPAC Name
(2-{4-[(2-butyl-1-benzofuran-3-yl)carbonyl]-2,6-diiodophenoxy}ethyl)diethylamine
SMILES
CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=CC=CC=C2O1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
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
Pharmacology
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
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Bedford laboratories
  • Ben venue laboratories inc
  • Bioniche pharma usa llc
  • Claris lifesciences ltd
  • Gland pharma ltd
  • Hikma farmaceutica (portugal) sa
  • Hospira inc
  • International medication systems ltd
  • Teva parenteral medicines inc
  • Wockhardt ltd
  • Wyeth pharmaceuticals inc
  • Prism pharmaceuticals inc
  • Apotex corp
  • Aurosal pharmaceuticals llc
  • Barr laboratories inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Taro pharmaceuticals usa inc
  • Teva pharmaceuticals usa inc
  • Teva pharmaceuticals usa
  • Zydus pharmaceuticals usa inc
  • Upsher smith laboratories inc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Solution Intravenous
Tablet Oral
Prices
Unit description Cost Unit
Amiodarone hcl powder 38.98 USD g
Pacerone 100 mg tablet 7.58 USD tablet
Pacerone 400 mg tablet 7.43 USD tablet
Amiodarone hcl 400 mg tablet 6.32 USD tablet
Cordarone 200 mg tablet 4.78 USD tablet
Pacerone 200 mg tablet 3.53 USD tablet
Amiodarone hcl 200 mg tablet 3.37 USD tablet
Cordarone 200 mg Tablet 2.32 USD tablet
Apo-Amiodarone 200 mg Tablet 1.3 USD tablet
Mylan-Amiodarone 200 mg Tablet 1.3 USD tablet
Novo-Amiodarone 200 mg Tablet 1.3 USD tablet
Pms-Amiodarone 200 mg Tablet 1.3 USD tablet
Ratio-Amiodarone 200 mg Tablet 1.3 USD tablet
Sandoz Amiodarone 200 mg Tablet 1.3 USD tablet
Amiodarone 150 mg/3 ml vial 0.83 USD ml
Pms-Amiodarone 100 mg Tablet 0.72 USD tablet
Amiodarone 900 mg/18 ml vial 0.59 USD ml
Amiodarone 450 mg/9 ml vial 0.57 USD ml
First Prev Next Last
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 7635773 2009-03-13 2029-03-13
United States 5134127 1993-01-23 2010-01-23
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
References
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
External Links
Resource Link
KEGG Drug D02910 Link_out
KEGG Compound C06823 Link_out
PubChem Compound 2157 Link_out
PubChem Substance 46507387 Link_out
ChemSpider 2072 Link_out
BindingDB 18957 Link_out
ChEBI 2663 Link_out
ChEMBL 2663 Link_out
Therapeutic Targets Database DAP000496 Link_out
PharmGKB PA448383 Link_out
IUPHAR 2566 Link_out
Guide to Pharmacology 2566 Link_out
Drug Product Database 2243836 Link_out
RxList http://www.rxlist.com/cgi/generic/amiodarone.htm Link_out
Drugs.com http://www.drugs.com/amiodarone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Amiodarone Link_out
ATC Codes
  • C01BD01
AHFS Codes
  • 24:04.04.20
PDB Entries Not Available
FDA label show (545 KB)
MSDS show (51.8 KB)
Interactions
Drug Interactions
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).
Food Interactions
  • Grapefruit and grapefruit juice should be avoided throughout treatment.
  • Grapefruit can significantly increase serum levels of this product.
  • Take without regard to meals.
Targets

1. Potassium voltage-gated channel subfamily H member 2

Pharmacological action: yes
Actions: inhibitor

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). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1

Organism class: human
UniProt ID: Q12809 Link_out
Gene: KCNH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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. Epub 2008 May 25. Pubmed
  3. 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. Pubmed
  4. 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. Epub 2008 Jul 7. Pubmed

2. Beta-1 adrenergic receptor

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P08588 Link_out
Gene: ADRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Doggrell SA, Brown L: Present and future pharmacotherapy for heart failure. Expert Opin Pharmacother. 2002 Jul;3(7):915-30. Pubmed

3. Voltage-dependent T-type calcium channel subunit alpha-1H

Pharmacological action: unknown
Actions: inhibitor

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. The isoform alpha-1H 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

Organism class: human
UniProt ID: O95180 Link_out
Gene: CACNA1H Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Epub 2010 Mar 10. Pubmed

4. Voltage-dependent calcium channel subunit alpha-2/delta-2

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: Q9NY47 Link_out
Gene: CACNA2D2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Epub 2010 Mar 10. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. 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. Pubmed

2. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Information Hyperlinked Over Proteins (iHOP) – Website
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. 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. Pubmed

3. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C9

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 1A2

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C19

Actions: substrate

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

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 1A1

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 3A5

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

9. Cytochrome P450 3A7

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor, inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19