Identification

Name
Digoxin
Accession Number
DB00390  (APRD00098)
Type
Small Molecule
Groups
Approved
Description

A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)

Structure
Thumb
Synonyms
  • 12beta-Hydroxydigitoxin
  • 12β-hydroxydigitoxin
  • 4-[(3S,5R,8R,9S,10S,12R,13S,14S)-3-[(2S,4S,5R,6R)-5-[(2S,4S,5R,6R)-5-[(2S,4S,5R,6R)-4,5-dihydroxy-6-methyl-oxan-2-yl]oxy-4-hydroxy-6-methyl-oxan-2-yl]oxy-4-hydroxy-6-methyl-oxan-2-yl]oxy-12,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-5H-furan-2-one
  • Digazolan
  • Digossina
  • Digoxin
  • Digoxina
  • Digoxine
  • Digoxinum
  • Lanadicor
External IDs
NSC-95100
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DigoxinSolution0.05 mg/1mLOralWest-Ward Pharmaceuticals Corp.2004-08-26Not applicableUs
DigoxinSolution0.05 mg/1mLOralAtlantic Biologicals Corps.2004-08-26Not applicableUs
DigoxinSolution0.05 mg/1mLOralPrecision Dose, Inc.2012-05-042019-05-31Us
DigoxinSolution0.05 mg/1mLOralPrecision Dose, Inc.2017-01-192019-04-30Us
Digoxin Injection C.S.D.Liquid0.5 mgIntramuscular; IntravenousSandoz Canada Incorporated1994-12-31Not applicableCanada
LanoxicapsCapsule, liquid filled200 ug/1OralGlaxosmithkline Inc1982-07-262008-06-30Us
LanoxicapsCapsule, liquid filled100 ug/1OralGlaxosmithkline Inc1982-07-262008-08-31Us
LanoxicapsCapsule, liquid filled100 ug/1OralPhysicians Total Care, Inc.2004-01-222011-05-31Us
LanoxinTablet125 ug/1OralMckesson Rxpak Inc2012-09-30Not applicableUs
LanoxinTablet250 ug/1OralMed Pharma Co., Ltd.1984-07-022012-05-21Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-digoxinTablet0.125 mgOralApotex Corporation2006-06-22Not applicableCanada
Apo-digoxinTablet0.25 mgOralApotex Corporation2006-06-22Not applicableCanada
Apo-digoxinTablet0.0625 mgOralApotex Corporation2006-06-22Not applicableCanada
DigitekTablet0.25 mg/1OralMylan Institutional2015-05-06Not applicableUs
DigitekTablet0.125 mg/1OralMylan Pharmaceuticals Inc.2014-11-17Not applicableUs
DigitekTablet0.125 mg/1OralMylan Institutional2015-05-06Not applicableUs
DigitekTablet0.25 mg/1OralMylan Pharmaceuticals Inc.2014-11-17Not applicableUs
DigoxTablet250 ug/1OralLake Erie Medical Dba Quality Care Produts Llc2002-07-26Not applicableUs
DigoxTablet125 ug/1OralSt. Marys Medical Park Pharmacy2013-05-022017-06-30Us
DigoxTablet125 ug/1OralLannett Company, Inc.2002-07-26Not applicableUs0527 132420180907 15195 109t07y
International/Other Brands
Agoxin (Aristopharma) / Cardiacin (Center) / Cardiogoxin (Medipharma) / Cardioxin (Oboi) / Cardoxin / Celoxin (Celon) / Centoxin (Opsonin) / Digacin (mibe) / Digocard-G (Klonal) / Digoxina (GlaxoSmithKline) / Eudigox (Teofarma) / Lanacordin (Kern) / Lanacrist / Lanicor (Roche) / Lanoxicaps / Lenoxin (GlaxoSmithKline)
Categories
UNII
73K4184T59
CAS number
20830-75-5
Weight
Average: 780.9385
Monoisotopic: 780.429606756
Chemical Formula
C41H64O14
InChI Key
LTMHDMANZUZIPE-PUGKRICDSA-N
InChI
InChI=1S/C41H64O14/c1-19-36(47)28(42)15-34(50-19)54-38-21(3)52-35(17-30(38)44)55-37-20(2)51-33(16-29(37)43)53-24-8-10-39(4)23(13-24)6-7-26-27(39)14-31(45)40(5)25(9-11-41(26,40)48)22-12-32(46)49-18-22/h12,19-21,23-31,33-38,42-45,47-48H,6-11,13-18H2,1-5H3/t19-,20-,21-,23-,24+,25-,26-,27+,28+,29+,30+,31-,33+,34+,35+,36-,37-,38-,39+,40+,41+/m1/s1
IUPAC Name
4-[(1S,2S,5S,7R,10R,11S,14R,15S,16R)-5-{[(2R,4S,5S,6R)-5-{[(2S,4S,5S,6R)-5-{[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy}-4-hydroxy-6-methyloxan-2-yl]oxy}-4-hydroxy-6-methyloxan-2-yl]oxy}-11,16-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]-2,5-dihydrofuran-2-one
SMILES
[H][C@]12CC[C@]3([H])[C@]([H])(C[C@@H](O)[C@]4(C)[C@H](CC[C@]34O)C3=CC(=O)OC3)[C@@]1(C)CC[C@@H](C2)O[C@H]1C[C@H](O)[C@H](O[C@H]2C[C@H](O)[C@H](O[C@H]3C[C@H](O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1

Pharmacology

Indication

For the treatment and management of congestive cardiac insufficiency, arrhythmias and heart failure.

Associated Conditions
Pharmacodynamics

Digoxin, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation.

Mechanism of action

Digoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium. The sodium calcium exchanger (NCX)in turn tries to extrude the sodium and in so doing, pumps in more calcium. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.

TargetActionsOrganism
ASodium/potassium-transporting ATPase subunit alpha-1Not AvailableHuman
Absorption

Absorption of digoxin from the elixir pediatric formulation has been demonstrated to be 70% to 85% complete (90% to 100% from the capsules, and 60% to 80% for tablets).

Volume of distribution
Not Available
Protein binding

25%

Metabolism

Hepatic (but not dependent upon the cytochrome P-450 system). The end metabolites, which include 3 b-digoxigenin, 3-keto-digoxigenin, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation.

Route of elimination

Following intravenous administration to healthy volunteers, 50% to 70% of a digoxin dose is excreted unchanged in the urine.

Half life

3.5 to 5 days

Clearance
Not Available
Toxicity

Toxicity includes ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block. LD50 = 7.8 mg/kg (orally in mice).

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Digoxin can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Digoxin can be decreased when combined with (S)-Warfarin.
16-BromoepiandrosteroneThe metabolism of Digoxin can be decreased when combined with 16-Bromoepiandrosterone.
1alpha-Hydroxyvitamin D5The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when 1alpha-Hydroxyvitamin D5 is combined with Digoxin.
3,5-diiodothyropropionic acidThe metabolism of Digoxin can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Digoxin.
5-androstenedioneThe metabolism of Digoxin can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Digoxin can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Digoxin can be decreased when combined with 6-O-benzylguanine.
AbacavirAbacavir may decrease the excretion rate of Digoxin which could result in a higher serum level.
Food Interactions
  • Avoid avocado.
  • Avoid bran and high fiber foods within 2 hours of taking this medication.
  • Avoid excess salt/sodium unless otherwise instructed by your physician.
  • Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
  • Avoid salt substitutes containing potassium.
  • Limit garlic, ginger, gingko, and horse chestnut.

References

Synthesis Reference

Wolfgang Voigtlander, Fritz Kaiser, Wolfgang Schaumann, Kurt Stach, "Preparation of C22-alkyl derivative of digoxin." U.S. Patent US3981862, issued October, 1972.

US3981862
General References
  1. Thompson DF, Carter JR: Drug-induced gynecomastia. Pharmacotherapy. 1993 Jan-Feb;13(1):37-45. [PubMed:8094898]
  2. Doering W, Konig E, Sturm W: [Digitalis intoxication: specifity and significance of cardiac and extracardiac symptoms. part I: Patients with digitalis-induced arrhythmias (author's transl)]. Z Kardiol. 1977 Mar;66(3):121-8. [PubMed:857452]
  3. Kaplanski J, Weinhouse E, Topaz M, Genchik G: Verapamil and digoxin: interactions in the rat. Res Commun Chem Pathol Pharmacol. 1983 Dec;42(3):377-88. [PubMed:6665298]
  4. Flanagan RJ, Jones AL: Fab antibody fragments: some applications in clinical toxicology. Drug Saf. 2004;27(14):1115-33. [PubMed:15554746]
External Links
Human Metabolome Database
HMDB0001917
KEGG Drug
D00298
KEGG Compound
C06956
PubChem Compound
2724385
PubChem Substance
46508524
ChemSpider
2006532
BindingDB
46355
ChEBI
4551
ChEMBL
CHEMBL1751
Therapeutic Targets Database
DAP000744
PharmGKB
PA449319
HET
DGX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Digoxin
ATC Codes
C01AA05 — Digoxin
AHFS Codes
  • 24:04.08 — Cardiotonic Agents
PDB Entries
1igj / 3b0w / 4ret
FDA label
Download (563 KB)
MSDS
Download (74.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingDiagnosticOrthostatic Intolerance / Postural Orthostatic Tachycardia Syndrome (POTS) / POTS1
1Active Not RecruitingOtherNeoplasms1
1Active Not RecruitingTreatmentNeoplasms1
1CompletedNot AvailableDrug-drug Interaction Study1
1CompletedNot AvailableHealthy Volunteers3
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of Digoxin1
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of Digoxin / Pharmacokinetics of Isavuconazole1
1CompletedNot AvailableHypertension,Essential1
1CompletedNot AvailablePharmacokinetic Interactions1
1CompletedBasic ScienceChemotherapy-Induced Nausea and Vomiting (CINV)1
1CompletedBasic ScienceCytomegalovirus (CMV)1
1CompletedBasic ScienceDepression1
1CompletedBasic ScienceDiabetes Mellitus (DM) / Healthy Volunteers1
1CompletedBasic ScienceDrug Interaction Potentiation1
1CompletedBasic ScienceDrug-Drug Interaction (DDI) / Healthy Volunteers / Pharmacokinetics1
1CompletedBasic ScienceEpilepsies1
1CompletedBasic ScienceHealthy Volunteers5
1CompletedBasic ScienceHealthy Volunteers / Pharmacokinetics1
1CompletedBasic ScienceHealthy Volunteers / Rheumatoid Arthritis1
1CompletedBasic ScienceN/A - Healthy Subjects1
1CompletedBasic ScienceRheumatoid Arthritis1
1CompletedOtherHealthy Volunteers4
1CompletedOtherHealthy Volunteers / Rheumatoid Arthritis1
1CompletedOtherTumors, Solid1
1CompletedTreatmentAlzheimer's Disease (AD) / Huntington's Disease (HD)1
1CompletedTreatmentCancer, Breast / Metastatic ErbB2 / Neoplasms, Breast1
1CompletedTreatmentDiabetes Mellitus (DM) / Healthy Volunteers2
1CompletedTreatmentEpilepsies1
1CompletedTreatmentHealthy Volunteers16
1CompletedTreatmentHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHepatitis C Virus (HCV)1
1CompletedTreatmentHereditary Angioedema1
1CompletedTreatmentInfluenza in Humans1
1CompletedTreatmentJapanese Healthy Adult Males1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1CompletedTreatmentMalignant Melanoma, Neoplasms1
1CompletedTreatmentNonvalvular Atrial Fibrillation1
1CompletedTreatmentType 2 Diabetes Mellitus3
1CompletedTreatmentType2 Diabetes Mellitus1
1CompletedTreatmentCMET-dysregulated Advanced Solid Tumors1
1Not Yet RecruitingPreventionInflammatory Responses1
1Not Yet RecruitingTreatmentFamilial Polycythemia1
1Not Yet RecruitingTreatmentHeathy Volunteer1
1WithdrawnTreatmentHealthy Volunteers1
1WithdrawnTreatmentMelanoma1
1, 2Not Yet RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
1, 2RecruitingTreatmentHead and Neck Carcinoma1
2Active Not RecruitingBasic ScienceCancer, Breast1
2CompletedTreatmentCutaneous Warts1
2CompletedTreatmentProstate Cancer1
2Not Yet RecruitingTreatmentActinic Keratosis (AK)1
2RecruitingTreatmentClassic Kaposi' s Sarcoma / Endemic Kaposi' s Sarcoma / Kaposi s Sarcoma (KS) / Lymph Angio Proliferations1
2TerminatedTreatmentMetastatic Breast Cancer (MBC)1
2, 3RecruitingTreatmentProstate Cancer1
3CompletedTreatmentArrythmias / Cardiovascular Disease (CVD) / Heart Diseases / Nonvalvular Atrial Fibrillation1
3CompletedTreatmentPostoperative Atrial Fibrillation1
3CompletedTreatmentTachycardia, Supraventricular1
3Enrolling by InvitationTreatmentFetal Atrial Flutter Without Hydrops / Fetal Supraventricular Tachycardia With Hydrops / Fetal Supraventricular Tachycardia Without Hydrops1
3RecruitingTreatmentAcute Heart Failure (AHF)1
4Active Not RecruitingBasic ScienceHealthy Volunteers1
4CompletedBasic ScienceDrug reactions1
4CompletedTreatmentCardiac Failure1
4CompletedTreatmentHeart Failure, Unspecified1
4Not Yet RecruitingTreatmentBMI >30 kg/m2 / Metabolic Syndromes / Polycystic Ovarian Syndrome1
4RecruitingTreatmentPermanent Atrial Fibrillation1
4Unknown StatusTreatmentHeart Failure, Unspecified1
Not AvailableActive Not RecruitingTreatmentPulmonary Hypertension (PH)1
Not AvailableCompletedNot AvailableCardiac Failure With Sinus Rhythm or Atrial Fibrillation / Heart Failure, Unspecified / Nonvalvular Atrial Fibrillation1
Not AvailableCompletedNot AvailablePregnancy Termination2
Not AvailableCompletedTreatmentArrythmias / Nonvalvular Atrial Fibrillation1
Not AvailableCompletedTreatmentHeart Diseases1
Not AvailableCompletedTreatmentHeart Failure, Unspecified1
Not AvailableRecruitingTreatmentNonvalvular Atrial Fibrillation1
Not AvailableUnknown StatusNot AvailableNonvalvular Atrial Fibrillation1

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline llc
  • Roxane laboratories inc
  • Abraxis pharmaceutical products
  • Baxter healthcare corp anesthesia and critical care
  • Hospira inc
  • Sandoz canada inc
  • Wyeth ayerst laboratories
  • Actavis totowa llc
  • Caraco pharmaceutical laboratories ltd
  • Impax laboratories inc
  • Jerome stevens pharmaceuticals inc
  • West ward pharmaceutical corp
  • Smithkline beecham corp dba glaxosmithkline
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Baxter International Inc.
  • C.O. Truxton Inc.
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Draxis Specialty Pharmaceuticals Inc.
  • DSM Corp.
  • Duramed
  • General Injectables and Vaccines Inc.
  • GlaxoSmithKline Inc.
  • Global Pharmaceuticals
  • Heartland Repack Services LLC
  • Hospira Inc.
  • Jerome Stevens Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • Kraft Pharmaceutical Co. Inc.
  • Lake Erie Medical and Surgical Supply
  • Lannett Co. Inc.
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Sandhills Packaging Inc.
  • Sandoz
  • Savage Labs
  • Southwood Pharmaceuticals
  • Spectrum Pharmaceuticals
  • Talbert Medical Management Corp.
  • UDL Laboratories
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • West-Ward Pharmaceuticals
Dosage forms
FormRouteStrength
InjectionIntramuscular; Intravenous0.25 mg/1.0mL
InjectionIntramuscular; Intravenous0.25 mg/1mL
Injection, solutionIntramuscular; Intravenous; Parenteral250 ug/1mL
SolutionOral0.05 mg/1mL
TabletOral0.125 mg/1
TabletOral0.125 mg/301
TabletOral0.25 mg/1
TabletOral0.25 mg/301
TabletOral0.250 mg/1
TabletOral125 ug/1
TabletOral250 ug/1
LiquidIntramuscular; Intravenous0.5 mg
Capsule, liquid filledOral100 ug/1
Capsule, liquid filledOral200 ug/1
Injection, solutionIntramuscular; Intravenous100 ug/1mL
Injection, solutionIntramuscular; Intravenous250 ug/1mL
TabletOral0.0625 mg/1
TabletOral0.1875 mg/1
LiquidOral.05 mg
LiquidIntramuscular; Intravenous.05 mg
LiquidIntramuscular; Intravenous.25 mg
TabletOral.0625 mg
TabletOral.125 mg
TabletOral.25 mg
LiquidIntramuscular; Intravenous0.05 mg
TabletOral0.25 mg
SolutionOral0.05 mg
TabletOral0.0625 mg
TabletOral0.125 mg
TabletOral0.250 mg
Prices
Unit descriptionCostUnit
Digibind 38 mg vial727.91USD vial
Digifab 40 mg vial615.6USD vial
Digoxin powder450.28USD g
Digoxin 0.05 mg/ml Solution 60ml Bottle36.99USD bottle
Lanoxin ped 0.1 mg/ml ampul6.91USD ml
Digoxin Pediatric 0.05 mg/ml6.79USD ml
Digoxin 0.25 mg/ml2.91USD ml
Lanoxin 0.25 mg/ml ampul1.44USD ml
Lanoxin 0.125 mg tablet0.73USD tablet
Lanoxin 0.25 mg tablet0.66USD tablet
Digoxin 0.125 mg tablet0.64USD tablet
Digoxin 0.25 mg tablet0.62USD tablet
Digoxin 0.25 mg/ml ampul0.61USD ml
Lanoxin Pediatric 0.05 mg/ml Elixir0.41USD ml
Lanoxicaps 0.1 mg capsule0.4USD capsule
Lanoxin 125 mcg tablet0.3USD tablet
Lanoxin 250 mcg tablet0.3USD tablet
Digitek 125 mcg tablet0.28USD tablet
Digitek 250 mcg tablet0.28USD tablet
Lanoxicaps 0.05 mg capsule0.28USD capsule
Toloxin 0.0625 mg Tablet0.27USD tablet
Toloxin 0.125 mg Tablet0.27USD tablet
Toloxin 0.25 mg Tablet0.27USD tablet
Digoxin 125 mcg tablet0.22USD tablet
Digoxin 250 mcg tablet0.22USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)217-221Stoll, A .and Kreis, W.; US.Patent 2,776,963; January 8,1957;assigned to Sandoz, AG, Switzerland.
water solubility64.8 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.26SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.127 mg/mLALOGPS
logP1.04ALOGPS
logP2.37ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)7.15ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area203.06 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity193.23 m3·mol-1ChemAxon
Polarizability84.8 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.941
Blood Brain Barrier-0.7241
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.8586
P-glycoprotein inhibitor INon-inhibitor0.5325
P-glycoprotein inhibitor IINon-inhibitor0.6209
Renal organic cation transporterNon-inhibitor0.8621
CYP450 2C9 substrateNon-substrate0.855
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7366
CYP450 1A2 substrateNon-inhibitor0.9261
CYP450 2C9 inhibitorNon-inhibitor0.9196
CYP450 2D6 inhibitorNon-inhibitor0.9359
CYP450 2C19 inhibitorNon-inhibitor0.9385
CYP450 3A4 inhibitorNon-inhibitor0.9279
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9279
Ames testNon AMES toxic0.9233
CarcinogenicityNon-carcinogens0.9668
BiodegradationNot ready biodegradable0.9555
Rat acute toxicity4.4721 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9818
hERG inhibition (predictor II)Inhibitor0.8051
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cardenolide glycosides and derivatives. These are compounds containing a carbohydrate glycosidically bound to the cardenolide moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid lactones
Direct Parent
Cardenolide glycosides and derivatives
Alternative Parents
Steroidal glycosides / Oligosaccharides / 12-hydroxysteroids / 14-hydroxysteroids / O-glycosyl compounds / Oxanes / Butenolides / Tertiary alcohols / Enoate esters / Secondary alcohols
show 8 more
Substituents
Cardanolide-glycoside / Steroidal glycoside / Oligosaccharide / 12-hydroxysteroid / 14-hydroxysteroid / Hydroxysteroid / Glycosyl compound / O-glycosyl compound / 2-furanone / Oxane
show 20 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
steroid saponin, cardenolide glycoside (CHEBI:4551) / cardanolide, Cardanolides and derivatives, Cardanolide and derivatives, Cardiac glycosides, Terpenoids (C06956)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Steroid hormone binding
Specific Function
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates th...
Gene Name
ATP1A1
Uniprot ID
P05023
Uniprot Name
Sodium/potassium-transporting ATPase subunit alpha-1
Molecular Weight
112895.01 Da
References
  1. Ravikumar A, Arun P, Devi KV, Augustine J, Kurup PA: Isoprenoid pathway and free radical generation and damage in neuropsychiatric disorders. Indian J Exp Biol. 2000 May;38(5):438-46. [PubMed:11272406]
  2. Chen JJ, Wang PS, Chien EJ, Wang SW: Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells. Br J Pharmacol. 2001 Apr;132(8):1761-8. [PubMed:11309248]
  3. Ke YS, Liu ZF, Yang H, Yang T, Huang JS, Rui SB, Cheng GH, Wang YX: Effect of anti-digoxin antiserum on endoxin and membrane ATPase activity in hypoxia-reoxygenation induced myocardial injury. Acta Pharmacol Sin. 2000 Apr;21(4):345-7. [PubMed:11324464]
  4. Kumar AR, Kurup PA: A hypothalamic digoxin mediated model for conscious and subliminal perception. J Neural Transm (Vienna). 2001;108(7):855-68. [PubMed:11515751]
  5. Aizman O, Uhlen P, Lal M, Brismar H, Aperia A: Ouabain, a steroid hormone that signals with slow calcium oscillations. Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13420-4. Epub 2001 Oct 30. [PubMed:11687608]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Gene Name
CYP11A1
Uniprot ID
P05108
Uniprot Name
Cholesterol side-chain cleavage enzyme, mitochondrial
Molecular Weight
60101.87 Da
References
  1. Chen JJ, Wang PS, Chien EJ, Wang SW: Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells. Br J Pharmacol. 2001 Apr;132(8):1761-8. [PubMed:11309248]
  2. Wang SW, Pu HF, Kan SF, Tseng CI, Lo MJ, Wang PS: Inhibitory effects of digoxin and digitoxin on corticosterone production in rat zona fasciculata-reticularis cells. Br J Pharmacol. 2004 Aug;142(7):1123-30. Epub 2004 Jul 12. [PubMed:15249423]
  3. Lin H, Wang SW, Tsai SC, Chen JJ, Chiao YC, Lu CC, Huang WJ, Wang GJ, Chen CF, Wang PS: Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450scc activity in rat testicular interstitial cells. Br J Pharmacol. 1998 Dec;125(8):1635-40. [PubMed:9886754]
Details
2. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Takara K, Tsujimoto M, Ohnishi N, Yokoyama T: Digoxin up-regulates MDR1 in human colon carcinoma Caco-2 cells. Biochem Biophys Res Commun. 2002 Mar 22;292(1):190-4. [PubMed:11890691]
  2. Takara K, Takagi K, Tsujimoto M, Ohnishi N, Yokoyama T: Digoxin up-regulates multidrug resistance transporter (MDR1) mRNA and simultaneously down-regulates steroid xenobiotic receptor mRNA. Biochem Biophys Res Commun. 2003 Jun 20;306(1):116-20. [PubMed:12788075]
  3. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389]
  4. Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. [PubMed:10746169]
  5. Yamazaki M, Neway WE, Ohe T, Chen I, Rowe JF, Hochman JH, Chiba M, Lin JH: In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results. J Pharmacol Exp Ther. 2001 Mar;296(3):723-35. [PubMed:11181899]
  6. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [PubMed:11785684]
  7. Neuhoff S, Ungell AL, Zamora I, Artursson P: pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions. Pharm Res. 2003 Aug;20(8):1141-8. [PubMed:12948010]
  8. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [PubMed:12948019]
  9. Dagenais C, Graff CL, Pollack GM: Variable modulation of opioid brain uptake by P-glycoprotein in mice. Biochem Pharmacol. 2004 Jan 15;67(2):269-76. [PubMed:14698039]
  10. Taipalensuu J, Tavelin S, Lazorova L, Svensson AC, Artursson P: Exploring the quantitative relationship between the level of MDR1 transcript, protein and function using digoxin as a marker of MDR1-dependent drug efflux activity. Eur J Pharm Sci. 2004 Jan;21(1):69-75. [PubMed:14706813]
  11. Tanigawara Y, Okamura N, Hirai M, Yasuhara M, Ueda K, Kioka N, Komano T, Hori R: Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J Pharmacol Exp Ther. 1992 Nov;263(2):840-5. [PubMed:1359120]
  12. Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM: Inhibition of P-glycoprotein-mediated drug transport: A unifying mechanism to explain the interaction between digoxin and quinidine [seecomments]. Circulation. 1999 Feb 2;99(4):552-7. [PubMed:9927403]
  13. Soldner A, Christians U, Susanto M, Wacher VJ, Silverman JA, Benet LZ: Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm Res. 1999 Apr;16(4):478-85. [PubMed:10227700]
  14. Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. [PubMed:15180340]
  15. Yamaguchi H, Yano I, Saito H, Inui K: Effect of cisplatin-induced acute renal failure on bioavailability and intestinal secretion of quinolone antibacterial drugs in rats. Pharm Res. 2004 Feb;21(2):330-8. [PubMed:15032316]
  16. Takara K, Sakaeda T, Kakumoto M, Tanigawara Y, Kobayashi H, Okumura K, Ohnishi N, Yokoyama T: Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport. Oncol Res. 2009;17(11-12):527-33. [PubMed:19806783]
  17. Jutabha P, Wempe MF, Anzai N, Otomo J, Kadota T, Endou H: Xenopus laevis oocytes expressing human P-glycoprotein: probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux. Pharmacol Res. 2010 Jan;61(1):76-84. doi: 10.1016/j.phrs.2009.07.002. Epub 2009 Jul 21. [PubMed:19631272]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ...
Gene Name
SLCO4C1
Uniprot ID
Q6ZQN7
Uniprot Name
Solute carrier organic anion transporter family member 4C1
Molecular Weight
78947.525 Da
References
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. [PubMed:14993604]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [PubMed:10224140]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Nishio T, Adachi H, Nakagomi R, Tokui T, Sato E, Tanemoto M, Fujiwara K, Okabe M, Onogawa T, Suzuki T, Nakai D, Shiiba K, Suzuki M, Ohtani H, Kondo Y, Unno M, Ito S, Iinuma K, Nunoki K, Matsuno S, Abe T: Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate. Biochem Biophys Res Commun. 2000 Sep 7;275(3):831-8. [PubMed:10973807]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. [PubMed:10617675]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Hagenbuch B, Adler ID, Schmid TE: Molecular cloning and functional characterization of the mouse organic-anion-transporting polypeptide 1 (Oatp1) and mapping of the gene to chromosome X. Biochem J. 2000 Jan 1;345 Pt 1:115-20. [PubMed:10600646]
  2. Noe B, Hagenbuch B, Stieger B, Meier PJ: Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10346-50. [PubMed:9294213]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood. Efficie...
Gene Name
SLC51A
Uniprot ID
Q86UW1
Uniprot Name
Organic solute transporter subunit alpha
Molecular Weight
37734.575 Da
References
  1. Seward DJ, Koh AS, Boyer JL, Ballatori N: Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta. J Biol Chem. 2003 Jul 25;278(30):27473-82. Epub 2003 Apr 28. [PubMed:12719432]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood. Efficie...
Gene Name
SLC51B
Uniprot ID
Q86UW2
Uniprot Name
Organic solute transporter subunit beta
Molecular Weight
14346.195 Da
References
  1. Seward DJ, Koh AS, Boyer JL, Ballatori N: Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta. J Biol Chem. 2003 Jul 25;278(30):27473-82. Epub 2003 Apr 28. [PubMed:12719432]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and of estrone-3-sulfate and taurocholate.
Gene Name
SLCO4A1
Uniprot ID
Q96BD0
Uniprot Name
Solute carrier organic anion transporter family member 4A1
Molecular Weight
77192.505 Da
References
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. [PubMed:14993604]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [PubMed:11159893]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-gluc...
Gene Name
SLCO1C1
Uniprot ID
Q9NYB5
Uniprot Name
Solute carrier organic anion transporter family member 1C1
Molecular Weight
78695.625 Da
References
  1. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. [PubMed:12351693]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. van Montfoort JE, Schmid TE, Adler ID, Meier PJ, Hagenbuch B: Functional characterization of the mouse organic-anion-transporting polypeptide 2. Biochim Biophys Acta. 2002 Aug 19;1564(1):183-8. [PubMed:12101011]
  2. Dagenais C, Ducharme J, Pollack GM: Uptake and efflux of the peptidic delta-opioid receptor agonist. Neurosci Lett. 2001 Apr 6;301(3):155-8. [PubMed:11257421]
  3. Sugiyama D, Kusuhara H, Shitara Y, Abe T, Meier PJ, Sekine T, Endou H, Suzuki H, Sugiyama Y: Characterization of the efflux transport of 17beta-estradiol-D-17beta-glucuronide from the brain across the blood-brain barrier. J Pharmacol Exp Ther. 2001 Jul;298(1):316-22. [PubMed:11408557]
  4. Hagenbuch N, Reichel C, Stieger B, Cattori V, Fattinger KE, Landmann L, Meier PJ, Kullak-Ublick GA: Effect of phenobarbital on the expression of bile salt and organic anion transporters of rat liver. J Hepatol. 2001 Jun;34(6):881-7. [PubMed:11451172]
  5. Gao B, Wenzel A, Grimm C, Vavricka SR, Benke D, Meier PJ, Reme CE: Localization of organic anion transport protein 2 in the apical region of rat retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2002 Feb;43(2):510-4. [PubMed:11818398]
  6. Shitara Y, Sugiyama D, Kusuhara H, Kato Y, Abe T, Meier PJ, Itoh T, Sugiyama Y: Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm Res. 2002 Feb;19(2):147-53. [PubMed:11883641]

Drug created on June 13, 2005 07:24 / Updated on October 15, 2018 04:36