Identification

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

Digoxin is one of the oldest cardiovascular medications used today.5 It is a common agent used to manage atrial fibrillation and the symptoms of heart failure.7 Digoxin is classified as a cardiac glycoside and was initially approved by the FDA in 1954.Label

This drug originates from the foxglove plant, also known as the Digitalis plant21, studied by William Withering, an English physician and botanist in the 1780s.8,9 Prior to this, a Welsh family, historically referred to as the Physicians of Myddvai, formulated drugs from this plant. They were one of the first to prescribe cardiac glycosides, according to ancient literature dating as early as the 1250s.9

Structure
Thumb
Synonyms
  • 12β-hydroxydigitoxin
  • Digossina
  • Digoxin
  • Digoxina
  • Digoxine
  • Digoxinum
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/1mLOralPrecision Dose, Inc.2012-05-042019-05-31Us
DigoxinSolution0.05 mg/1mLOralAtlantic Biologicals Corps.2004-08-26Not applicableUs
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 filled100 ug/1OralPhysicians Total Care, Inc.2004-01-222011-05-31Us
LanoxicapsCapsule, liquid filled200 ug/1OralGlaxosmithkline Inc1982-07-262008-06-30Us
LanoxicapsCapsule, liquid filled100 ug/1OralGlaxosmithkline Inc1982-07-262008-08-31Us
LanoxinTablet0.125 mgOralPharmascience Inc2001-03-162016-11-24Canada
LanoxinInjection, solution250 ug/1mLIntramuscular; IntravenousGlaxosmithkline Inc1985-10-012014-03-31Us
Additional Data Available
  • Application Number
    Application Number

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-digoxinTablet0.125 mgOralApotex Corporation2006-06-22Not applicableCanada
Apo-digoxinTablet0.0625 mgOralApotex Corporation2006-06-22Not applicableCanada
Apo-digoxinTablet0.25 mgOralApotex Corporation2006-06-22Not applicableCanada
DigitekTablet0.25 mg/1OralMylan Institutional Inc.2015-05-06Not applicableUs
DigitekTablet0.125 mg/1OralMylan Institutional Inc.2015-05-06Not applicableUs
DigitekTablet0.125 mg/1OralMylan Pharmaceuticals Inc.2014-11-17Not applicableUs
DigitekTablet0.25 mg/1OralMylan Pharmaceuticals Inc.2014-11-17Not applicableUs
DigoxTablet250 ug/1OralA-S Medication Solutions2002-07-26Not applicableUs50090 096220180907 15195 1vjp40p
DigoxTablet125 ug/1OralTYA Pharmaceuticals2002-07-26Not applicableUs00527 1324 10 nlmimage10 bf055fda
DigoxTablet250 ug/1OralCarilion Materials Management2002-07-26Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Agoxin (Aristopharma) / Cardiacin (Center) / Cardiogoxin (Medipharma) / Cardioxin (Oboi) / Cardoxin / Celoxin (Celon) / Centoxin (Opsonin) / Digacin (mibe) / Digazolan / Digocard-G (Klonal) / Digoxina (GlaxoSmithKline) / Eudigox (Teofarma) / Lanacordin (Kern) / Lanacrist / Lanadicor / Lanicor (Roche) / 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

Digoxin is indicated in the following conditions:

1) For the treatment of mild to moderate heart failure in adult patients.Label 2) To increase myocardial contraction in children diagnosed with heart failure.Label 3) To maintain control ventricular rate in adult patients diagnosed with chronic atrial fibrillation.Label

In adults with heart failure, when it is clinically possible, digoxin should be administered in conjunction with a diuretic and an angiotensin-converting enzyme (ACE) inhibitor for optimum effects.Label

Associated Conditions
Associated Therapies
Pharmacodynamics

General effects

Digoxin is a positive inotropic and negative chronotropic drug7, meaning that it increases the force of the heartbeat and decreases the heart rate.23 The decrease in heart rate is particularly useful in cases of atrial fibrillation, a condition characterized by a fast and irregular heartbeat.13 Peak effects of digoxin on the cardiovascular system are attained between 3-6 hours following a single dose and can last for 24 hours or more.Label

Digoxin enhances the contractile force of the heart muscle by blocking ATPase enzyme activity, which controls the movement of calcium, sodium, and potassium into the myocardium. Increased calcium interaction with the cardiac muscle increases contractile strength, improving the left ventricular ejection fraction (EF), an important measure of cardiac function.7,22 The relief of heart failure symptoms during digoxin therapy has been demonstrated in clinical studies by increased exercise capacity and reduced hospitalization due to heart failure and reduced heart failure-related emergency medical visits.Label

A note on cardiovascular risk

The decreased refractory period of the cardiac action potential caused by digoxin leads to increased automaticity, or the ability of the heart to spontaneously depolarize and cause an action potential, leading to a contraction and/or arrhythmia.11,20 Digoxin poses a risk of rapid ventricular response that can cause ventricular fibrillation in patients with an accessory atrioventricular (AV) pathway. Cardiac arrest as a result of ventricular fibrillation is fatal.Label An increased risk of fatal severe or complete heart block is present in individuals with pre-existing sinus node disease and AV block who take digoxin. Exercise caution in these patients, and titrate the dose of digoxin slowly.Label The emergence of new-onset Mobitz type 1 AV block, accelerated junctional rhythm, non-paroxysmal atrial tachycardia accompanied by AV block, and bi-directional ventricular tachycardia may be observed during digoxin therapy.Label

Effects on the sympathetic nervous system and potassium

Digoxin has a narrow therapeutic window. At higher concentrations, digoxin increases sympathetic output from the central nervous system to nerves in the cardiovascular system Label,18 In addition to this, higher doses of digoxin may result in the enhanced efflux of potassium from cells, leading to increases in serum potassium levels that may predispose to arrhythmia.Label This occurs through skeletal muscle receptor binding by excess digoxin, likely displacing potassium into the circulation.17

Mechanism of action

Digoxin exerts hemodynamic, electrophysiologic, and neurohormonal effects on the cardiovascular system.7 It reversibly inhibits the Na-K ATPase enzyme, leading to various beneficial effects. The Na-K ATPase enzyme functions to maintain the intracellular environment by regulating the entry and exit of sodium, potassium, and calcium (indirectly). Na-K ATPase is also known as the sodium pumpLabel. The inhibition of the sodium pump by digoxin increases intracellular sodium and increases the calcium level in the myocardial cells, causing an increased strength of heart contraction.Label,11 Digoxin affects the sodium-potassium exchange mechanism of cells in the autonomic nervous system in a similar manner. This leads to decreased cardiac impulse conduction through the atria and atrioventricular node (AV node), decreasing heart rate.24

Digoxin also stimulates the parasympathetic nervous system via the vagus nerve20 leading to sinoatrial (SA) and atrioventricular (AV) node effects, decreasing the heart rate.Label,7 Part of the pathophysiology of heart failure includes neurohormonal activation, leading to an increase in norepinephrine. Digoxin helps to decrease norepinephrine levels through activation of the parasympathetic nervous system.7

TargetActionsOrganism
ASodium/potassium-transporting ATPase subunit alpha-1
inhibitor
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

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Absorption

Digoxin is approximately 70-80% absorbed in the first part of the small bowel.6 The bioavailability of an oral dose varies from 50-90%, however, oral gelatinized capsules of digoxin are reported to have a bioavailability of 100%.10 Tmax, or the time to reach the maximum concentration of digoxin was measured to be 1.0 h in one clinical study of healthy patients taking 0.25 mg of digoxin with a placebo.19 Cmax, or maximum concentration, was 1.32 ± 0.18 ng/ml−1 in the same study, and AUC (area under the curve) was 12.5 ± 2.38 ng/ml−1.19 If digoxin is ingested after a meal, absorption is slowed but this does not change the total amount of absorbed drug. If digoxin is taken with meals that are in fiber, absorption may be decreased.24

A note on gut bacteria

An oral dose of digoxin may be transformed into pharmacologically inactive products by bacteria in the colon. Studies have indicated that 10% of patients receiving digoxin tablets will experience the degradation of at least 40% of an ingested dose of digoxin by gut bacteria. Several antibiotics may increase the absorption of digoxin in these patients, due to the elimination of gut bacteria, which normally cause digoxin degradation.Label

A note on malabsorption

Patients with malabsorption due to a variety of causes may have a decreased ability to absorb digoxin.Label P-glycoprotein, located on cells in the intestine, may interfere with digoxin pharmacokinetics, as it is a substrate of this efflux transporter. P-glycoprotein can be induced by other drugs, therefore reducing the effects of digoxin by increasing its efflux in the intestine.Label

Volume of distribution

This drug is widely distributed in the body, and is known to cross the blood-brain barrier and the placenta.Label,6 The apparent volume of distribution of digoxin is 475-500 L.Label A large portion of digoxin is distributed in the skeletal muscle followed by the heart and kidneys.6 It is important to note that the elderly population, generally having a decreased muscle mass, may show a lower volume of digoxin distribution.Label

Protein binding

Digoxin protein binding is approximately 25%.Label It is mainly bound to albumin.6

Metabolism

About 13% of a digoxin dose is found to be metabolized in healthy subjects. Several urinary metabolites of digoxin exist, including dihydrodigoxin and digoxigenin bisdigitoxoside. Their glucuronidated and sulfated conjugates are thought to be produced through the process of hydrolysis, oxidation, and additionally, conjugation. The cytochrome P-450 system does not play a major role in digoxin metabolism, nor does this drug induce or inhibit the enzymes in this system.Label

Route of elimination

The elimination of digoxin is proportional to the total dose, following first order kinetics. After intravenous (IV) administration to healthy subjects, 50-70% of the dose is measured excreted as unchanged digoxin in the urine. Approximately 25 to 28% of digoxin is eliminated outside of the kidney. Biliary excretion appears to be of much less importance than renal excretion.6

Digoxin is not effectively removed from the body by dialysis, exchange transfusion, or during cardiopulmonary bypass because most of the drug is bound to extravascular tissues.Label

Half life

Digoxin has a half-life of 1.5-2 days in healthy subjects.Label The half-life in patients who do not pass urine, usually due to renal failure, is prolonged to 3.5-5 days. Since most of the drug is distributed extravascularly, dialysis and exchange transfusion are not optimal methods for the removal of digoxin.Label

Clearance

The clearance of digoxin closely correlates to creatinine clearance, and does not depend on urinary flow. Individuals with renal impairment or failure may exhibit extensively prolonged half-lives. It is therefore important to titrate the dose accordingly and regularly monitor serum digoxin levels.Label One pharmacokinetic study measured the mean body clearance of intravenous digoxin to be 88 ± 44ml/min/l.73 m².16 Another study provided mean clearance values of 53 ml/min/1.73 m² in men aged 73-81 and 83 ml/min/1.73 m² in men aged 20-33 years old after an intravenous digoxin dose.15

Toxicity

Oral TDLO (human female): 100 ug/kg, Oral TDLO (human male): 75 ug/kg, Oral LD50 (rat): 28270 ug/kgMSDS

Summary of toxicity

Digoxin toxicity can occur in cases of supratherapeutic dose ingestion or as a result of chronic overexposure.20 Digoxin toxicity may be manifested by symptoms of nausea, vomiting, visual changes, in addition to arrhythmia. Older age, lower body weight, and decreased renal function or electrolyte abnormalities lead to an increased risk of digoxin toxicity.Label

Cardiac toxicity contributes to approximately 1/2 of adverse events caused by digoxin. Gastrointestinal toxicity accounts for about 1/4, and central nervous system and other toxicities represent about 1/4 of reported adverse events.Label

Pregnancy

This drug is a pregnancy category C drug, showing negative effects on the fetus in animal studies. No studies have been done to evaluate the use of digoxin in human pregnancy. It should not be given to pregnant women unless it is clearly required.Label

Nursing

Digoxin is distributed to human breastmilk, with a milk to serum concentration ratio of 0.6-0.9. The usual maintenance dose does not amount to significant concentrations in the infant, therefore, digoxin may be used at normal maintenance doses during nursing.Label

Carcinogenesis and mutagenesis

No genotoxic potential was identified during in vitro studies (including the Ames test and mouse lymphoma assay) when digoxin was used. There are no data available currently regarding the carcinogenic potential of this drug.Label

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

Interactions

Drug Interactions
DrugInteraction
1alpha-Hydroxyvitamin D5The risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when 1alpha-Hydroxyvitamin D5 is combined with Digoxin.
6-Deoxyerythronolide BThe serum concentration of Digoxin can be increased when it is combined with 6-Deoxyerythronolide B.
AbacavirAbacavir may decrease the excretion rate of Digoxin which could result in a higher serum level.
AbaloparatideThe serum concentration of Digoxin can be increased when it is combined with Abaloparatide.
AbataceptThe metabolism of Digoxin can be increased when combined with Abatacept.
AbemaciclibAbemaciclib may decrease the excretion rate of Digoxin which could result in a higher serum level.
AbexinostatThe risk or severity of QTc prolongation can be increased when Digoxin is combined with Abexinostat.
AcarboseThe serum concentration of Digoxin can be decreased when it is combined with Acarbose.
AcebutololAcebutolol may increase the bradycardic activities of Digoxin.
AceclofenacAceclofenac may decrease the excretion rate of Digoxin which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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    Evidence Level

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  • Action
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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]
  5. MacLeod-Glover N, Mink M, Yarema M, Chuang R: Digoxin toxicity: Case for retiring its use in elderly patients? Can Fam Physician. 2016 Mar;62(3):223-8. [PubMed:26975913]
  6. Iisalo E: Clinical pharmacokinetics of digoxin. Clin Pharmacokinet. 1977 Jan-Feb;2(1):1-16. doi: 10.2165/00003088-197702010-00001. [PubMed:322907]
  7. Ziff OJ, Kotecha D: Digoxin: The good and the bad. Trends Cardiovasc Med. 2016 Oct;26(7):585-95. doi: 10.1016/j.tcm.2016.03.011. Epub 2016 Mar 31. [PubMed:27156593]
  8. Whayne TF Jr: Clinical Use of Digitalis: A State of the Art Review. Am J Cardiovasc Drugs. 2018 Dec;18(6):427-440. doi: 10.1007/s40256-018-0292-1. [PubMed:30066080]
  9. Norn S, Kruse PR: [Cardiac glycosides: From ancient history through Withering's foxglove to endogeneous cardiac glycosides]. Dan Medicinhist Arbog. 2004:119-32. [PubMed:15685783]
  10. Currie GM, Wheat JM, Kiat H: Pharmacokinetic considerations for digoxin in older people. Open Cardiovasc Med J. 2011;5:130-5. doi: 10.2174/1874192401105010130. Epub 2011 Jun 15. [PubMed:21769303]
  11. Mangoni ME, Nargeot J: Genesis and regulation of the heart automaticity. Physiol Rev. 2008 Jul;88(3):919-82. doi: 10.1152/physrev.00018.2007. [PubMed:18626064]
  12. Vincent JL: Understanding cardiac output. Crit Care. 2008;12(4):174. doi: 10.1186/cc6975. Epub 2008 Aug 22. [PubMed:18771592]
  13. Gutierrez C, Blanchard DG: Diagnosis and Treatment of Atrial Fibrillation. Am Fam Physician. 2016 Sep 15;94(6):442-52. [PubMed:27637120]
  14. Virgadamo S, Charnigo R, Darrat Y, Morales G, Elayi CS: Digoxin: A systematic review in atrial fibrillation, congestive heart failure and post myocardial infarction. World J Cardiol. 2015 Nov 26;7(11):808-16. doi: 10.4330/wjc.v7.i11.808. [PubMed:26635929]
  15. Ewy GA, Kapadia GG, Yao L, Lullin M, Marcus FI: Digoxin metabolism in the elderly. Circulation. 1969 Apr;39(4):449-53. [PubMed:5778245]
  16. Koup JR, Jusko WJ, Elwood CM, Kohli RK: Digoxin pharmacokinetics: role of renal failure in dosage regimen design. Clin Pharmacol Ther. 1975 Jul;18(1):9-21. doi: 10.1002/cpt19751819. [PubMed:1149366]
  17. Schmidt TA, Bundgaard H, Olesen HL, Secher NH, Kjeldsen K: Digoxin affects potassium homeostasis during exercise in patients with heart failure. Cardiovasc Res. 1995 Apr;29(4):506-11. [PubMed:7796444]
  18. Watanabe Y, Okumura K, Hashimoto H, Ito T, Ogawa K, Satake T: Effects of digoxin on acetylcholine and norepinephrine concentrations in rat myocardium. J Cardiovasc Pharmacol. 1989 May;13(5):702-8. [PubMed:2472517]
  19. Schwartz JI, Agrawal NG, Wehling M, Musser BJ, Gumbs CP, Michiels N, De Smet M, Wagner JA: Evaluation of the pharmacokinetics of digoxin in healthy subjects receiving etoricoxib. Br J Clin Pharmacol. 2008 Dec;66(6):811-7. doi: 10.1111/j.1365-2125.2008.03285.x. Epub 2008 Sep 24. [PubMed:18823299]
  20. Rameez Rehman; Ofek Hai. (2018). Digitalis Toxicity. StatPearls Publishing.
  21. IARC Working Group on the Evaluation of Carcinogenic Risk to Humans. Lyon (FR) (2016). Some Drugs and Herbal Products. International Agency for Research on Cancer.
  22. A Kosaraju (2019). Left Ventricular Ejection Fraction. StatPearls.
  23. Digoxin pharmacokinetics [Link]
  24. MedSafe NZ: Lanoxin [Link]
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
Wikipedia
Digoxin
ATC Codes
C01AA05 — Digoxin
AHFS Codes
  • 24:04.08 — Cardiotonic Agents
PDB Entries
1igj / 3b0w / 4ret
FDA label
Download (581 KB)
MSDS
Download (29 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentCancer, Breast / Circulating Tumor Cells (CTCs)1
0RecruitingDiagnosticOrthostatic Intolerance / Postural Orthostatic Tachycardia Syndrome (POTS) / POTS1
1Active Not RecruitingOtherNeoplasms1
1Active Not RecruitingTreatmentDrug Drug Interaction (DDI)1
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 Drug Interaction (DDI) / Healthy Volunteers / Pharmacokinetics1
1CompletedBasic ScienceDrug Interaction Potentiation2
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
1CompletedTreatmentDrug Drug Interaction (DDI)1
1CompletedTreatmentEpilepsies1
1CompletedTreatmentHealthy Volunteers16
1CompletedTreatmentHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHeathy Volunteer1
1CompletedTreatmentHepatitis C Virus (HCV) Infection1
1CompletedTreatmentHereditary Angioedema1
1CompletedTreatmentInfluenza in Humans1
1CompletedTreatmentJapanese Healthy Adult Males1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1CompletedTreatmentMalignant Melanoma, Neoplasms1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentNonvalvular Atrial Fibrillation1
1CompletedTreatmentType 2 Diabetes Mellitus3
1CompletedTreatmentType2 Diabetes Mellitus1
1CompletedTreatmentCMET-dysregulated Advanced Solid Tumors1
1Not Yet RecruitingPreventionInflammatory Responses1
1Not Yet RecruitingTreatmentAdvanced Pancreatic Cancer / Advanced Solid Tumors1
1Not Yet RecruitingTreatmentFamilial Polycythemia1
1RecruitingTreatmentHealthy Volunteers1
1WithdrawnTreatmentHealthy Volunteers1
1WithdrawnTreatmentMelanoma1
1, 2RecruitingTreatmentHead and Neck Carcinoma1
1, 2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
2Active Not RecruitingBasic ScienceCancer, Breast1
2CompletedTreatmentCutaneous Warts1
2CompletedTreatmentProstate Cancer1
2RecruitingTreatmentActinic 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
3RecruitingTreatmentAcute Heart Failure (AHF)1
3RecruitingTreatmentFetal Atrial Flutter Without Hydrops / Fetal Supraventricular Tachycardia With Hydrops / Fetal Supraventricular Tachycardia Without Hydrops1
3RecruitingTreatmentHeart Diseases / Nonvalvular Atrial Fibrillation1
4Active Not RecruitingBasic ScienceHealthy Volunteers1
4CompletedBasic ScienceDrug reactions1
4CompletedOtherPregnancy termination therapy1
4CompletedTreatmentCardiac Failure1
4CompletedTreatmentHeart Failure1
4Not Yet RecruitingTreatmentHeart Failure1
4RecruitingTreatmentPermanent Atrial Fibrillation1
4Unknown StatusTreatmentHeart Failure1
Not AvailableActive Not RecruitingTreatmentNonvalvular Atrial Fibrillation1
Not AvailableActive Not RecruitingTreatmentPulmonary Hypertension (PH)1
Not AvailableCompletedNot AvailableCardiac Failure With Sinus Rhythm or Atrial Fibrillation / Heart Failure / Nonvalvular Atrial Fibrillation1
Not AvailableCompletedNot AvailablePregnancy Termination2
Not AvailableCompletedTreatmentArrythmias / Nonvalvular Atrial Fibrillation1
Not AvailableCompletedTreatmentHeart Diseases1
Not AvailableCompletedTreatmentHeart Failure1
Not AvailableNot Yet RecruitingNot AvailableCongenital Heart Disease (CHD)1
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/301
TabletOral0.125 mg/1
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)230-265https://monographs.iarc.fr/wp-content/uploads/2018/06/mono108-13.pdf
boiling point (°C)931.6https://www.lookchem.com/Digoxin/
water solubility64.8 mg/L (at 25 °C)https://monographs.iarc.fr/wp-content/uploads/2018/06/mono108-13.pdf
logP2.37http://www.t3db.ca/toxins/T3D2670
pKa-3, 7.15https://monographs.iarc.fr/wp-content/uploads/2018/06/mono108-13.pdf
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
Humans
Pharmacological action
Yes
Actions
Inhibitor
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]
  6. Rameez Rehman; Ofek Hai. (2018). Digitalis Toxicity. StatPearls Publishing.

Enzymes

Kind
Protein
Organism
Humans
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]

Transporters

Kind
Protein
Organism
Humans
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]
  18. Chan LM, Cooper AE, Dudley AL, Ford D, Hirst BH: P-glycoprotein potentiates CYP3A4-mediated drug disappearance during Caco-2 intestinal secretory detoxification. J Drug Target. 2004;12(7):405-13. doi: 10.1080/10611860412331285224 . [PubMed:15621665]
  19. Haslam IS, Jones K, Coleman T, Simmons NL: Induction of P-glycoprotein expression and function in human intestinal epithelial cells (T84). Biochem Pharmacol. 2008 Oct 1;76(7):850-61. doi: 10.1016/j.bcp.2008.07.020. Epub 2008 Jul 23. [PubMed:18703021]
  20. Riganti C, Campia I, Polimeni M, Pescarmona G, Ghigo D, Bosia A: Digoxin and ouabain induce P-glycoprotein by activating calmodulin kinase II and hypoxia-inducible factor-1alpha in human colon cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):385-92. doi: 10.1016/j.taap.2009.07.026. Epub 2009 Jul 30. [PubMed:19647009]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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]
  2. Yamaguchi H, Sugie M, Okada M, Mikkaichi T, Toyohara T, Abe T, Goto J, Hishinuma T, Shimada M, Mano N: Transport of estrone 3-sulfate mediated by organic anion transporter OATP4C1: estrone 3-sulfate binds to the different recognition site for digoxin in OATP4C1. Drug Metab Pharmacokinet. 2010;25(3):314-7. [PubMed:20610891]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Data regarding this transporter in relation to digoxin are limited in the literature. The results of one in vitro study suggest that this drug is transported by the bile salt export pump.
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. 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]
Kind
Protein
Organism
Humans
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
Humans
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]
  2. Ballatori N, Li N, Fang F, Boyer JL, Christian WV, Hammond CL: OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids. Front Biosci (Landmark Ed). 2009 Jan 1;14:2829-44. [PubMed:19273238]
  3. Malinen MM, Ali I, Bezencon J, Beaudoin JJ, Brouwer KLR: Organic solute transporter OSTalpha/beta is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury. Am J Physiol Gastrointest Liver Physiol. 2018 May 1;314(5):G597-G609. doi: 10.1152/ajpgi.00310.2017. Epub 2018 Feb 8. [PubMed:29420067]
Kind
Protein
Organism
Humans
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]
  2. Ballatori N, Li N, Fang F, Boyer JL, Christian WV, Hammond CL: OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids. Front Biosci (Landmark Ed). 2009 Jan 1;14:2829-44. [PubMed:19273238]
  3. Malinen MM, Ali I, Bezencon J, Beaudoin JJ, Brouwer KLR: Organic solute transporter OSTalpha/beta is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury. Am J Physiol Gastrointest Liver Physiol. 2018 May 1;314(5):G597-G609. doi: 10.1152/ajpgi.00310.2017. Epub 2018 Feb 8. [PubMed:29420067]
Kind
Protein
Organism
Humans
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 June 14, 2019 17:46