Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
Identification
NameDigitoxin
Accession NumberDB01396
Typesmall molecule
Groupsapproved
Description

A cardiac glycoside sometimes used in place of digoxin. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting. (From Martindale, The Extra Pharmacopoeia, 30th ed, p665)

Structure
Thumb
Synonyms
SynonymLanguageCode
DigitoksinNot AvailableNot Available
DigitoxinumNot AvailableNot Available
DigitoxosideNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
CrystodiginNot Available
TardigalNot Available
Brand mixturesNot Available
Categories
CAS number71-63-6
WeightAverage: 764.9391
Monoisotopic: 764.434692134
Chemical FormulaC41H64O13
InChI KeyInChIKey=WDJUZGPOPHTGOT-XUDUSOBPSA-N
InChI
InChI=1S/C41H64O13/c1-20-36(46)29(42)16-34(49-20)53-38-22(3)51-35(18-31(38)44)54-37-21(2)50-33(17-30(37)43)52-25-8-11-39(4)24(15-25)6-7-28-27(39)9-12-40(5)26(10-13-41(28,40)47)23-14-32(45)48-19-23/h14,20-22,24-31,33-38,42-44,46-47H,6-13,15-19H2,1-5H3/t20-,21-,22-,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,15R)-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-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-yl]-2,5-dihydrofuran-2-one
SMILES
[H][C@]12CC[C@]3([H])[C@]([H])(CC[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
Mass Specshow(12.6 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassSteroid Lactones
Direct parentCardenolide Glycosides and Derivatives
Alternative parentsTrihexoses; Steroidal Glycosides; Hydroxysteroids; O-glycosyl Compounds; Cyclohexanols; Oxanes; Butenolides; Tertiary Alcohols; 1,2-Diols; Carboxylic Acid Esters; Cyclic Alcohols and Derivatives; Acetals; Polyamines
Substituentssteroidal glycoside; 14-hydroxy-steroid; trisaccharide; o-glycosyl compound; glycosyl compound; cyclohexanol; oxane; 2-furanone; saccharide; tertiary alcohol; cyclic alcohol; dihydrofuran; carboxylic acid ester; 1,2-diol; secondary alcohol; ether; acetal; polyamine; carboxylic acid derivative; alcohol
Classification descriptionThis compound belongs to the cardenolide glycosides and derivatives. These are compounds containing a carbohydrate glycosidically bound to the cardenolide moiety.
Pharmacology
IndicationFor the treatment and management of congestive cardiac insufficiency, arrhythmias and heart failure.
PharmacodynamicsDigitoxin is a cardiac glycoside sometimes used in place of DIGOXIN. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting (From Martindale, The Extra Pharmacopoeia, 30th ed, p665). Unlike digoxin (which is eliminated from the body via the kidneys), it is eliminated via the liver, so could be used in patients with poor or erratic kidney function. However, it is now rarely used in current UK medical practice. While there have been several controlled trials which have shown digoxin to be effective in a proportion of patients treated for heart failure, there is not the same strong evidence base for digitoxin, although it is presumed to be similarly effective.
Mechanism of actionDigitoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digitoxin 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityDigitoxin exhibits similar toxic effects to the more-commonly used digoxin, namely: anorexia, nausea, vomiting, diarrhoea, confusion, visual disturbances, and cardiac arrhythmias.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9718
Blood Brain Barrier - 0.557
Caco-2 permeable - 0.8386
P-glycoprotein substrate Substrate 0.8528
P-glycoprotein inhibitor I Inhibitor 0.5557
P-glycoprotein inhibitor II Non-inhibitor 0.6021
Renal organic cation transporter Non-inhibitor 0.8473
CYP450 2C9 substrate Non-substrate 0.8687
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.7407
CYP450 1A2 substrate Non-inhibitor 0.8902
CYP450 2C9 substrate Non-inhibitor 0.9082
CYP450 2D6 substrate Non-inhibitor 0.9412
CYP450 2C19 substrate Non-inhibitor 0.9258
CYP450 3A4 substrate Non-inhibitor 0.901
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9381
Ames test Non AMES toxic 0.9233
Carcinogenicity Non-carcinogens 0.9637
Biodegradation Not ready biodegradable 0.9671
Rat acute toxicity 4.4764 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9812
hERG inhibition (predictor II) Inhibitor 0.7759
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
Packagers
Dosage forms
FormRouteStrength
LiquidOral
LiquidOral
Prices
Unit descriptionCostUnit
Digitoxin powder486.85USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point255.5 °CPhysProp
water solubility3.9 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.85SANGSTER (1993)
Predicted Properties
PropertyValueSource
water solubility2.89e-02 g/lALOGPS
logP2.33ALOGPS
logP3.6ChemAxon
logS-4.4ALOGPS
pKa (strongest acidic)7.18ChemAxon
pKa (strongest basic)0.24ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count12ChemAxon
hydrogen donor count5ChemAxon
polar surface area182.83ChemAxon
rotatable bond count7ChemAxon
refractivity191.72ChemAxon
polarizability83.58ChemAxon
number of rings8ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Belz GG, Breithaupt-Grogler K, Osowski U: Treatment of congestive heart failure—current status of use of digitoxin. Eur J Clin Invest. 2001;31 Suppl 2:10-7. Pubmed
  2. Kurowski V, Iven H, Djonlagic H: Treatment of a patient with severe digitoxin intoxication by Fab fragments of anti-digitalis antibodies. Intensive Care Med. 1992;18(7):439-42. Pubmed
  3. Johansson S, Lindholm P, Gullbo J, Larsson R, Bohlin L, Claeson P: Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells. Anticancer Drugs. 2001 Jun;12(5):475-83. Pubmed
  4. Hippius M, Humaid B, Sicker T, Hoffmann A, Gottler M, Hasford J: Adverse drug reaction monitoring—digitoxin overdosage in the elderly. Int J Clin Pharmacol Ther. 2001 Aug;39(8):336-43. Pubmed
External Links
ResourceLink
KEGG DrugD00297
KEGG CompoundC06955
PubChem Compound441207
PubChem Substance46506035
ChemSpider389987
ChEBI28544
ChEMBLCHEMBL254219
Therapeutic Targets DatabaseDAP000120
PharmGKBPA449316
Drug Product Database2236621
WikipediaDigitoxin
ATC CodesC01AA04
AHFS Codes
  • 92:02.00*
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.4 KB)
Interactions
Drug Interactions
Drug
BendroflumethiazidePossible electrolyte variations and arrhythmias
BumetanidePossible electrolyte variations and arrhythmias
ChlorthalidonePossible electrolyte variations and arrhythmias
Ethacrynic acidPossible electrolyte variations and arrhythmias
FurosemidePossible electrolyte variations and arrhythmias
HydrochlorothiazidePossible electrolyte variations and arrhythmias
IndapamidePossible electrolyte variations and arrhythmias
MetolazonePossible electrolyte variations and arrhythmias
QuinidineQuinine/quinidine increases the effect of digoxin
QuinineQuinine/quinidine increases the effect of digoxin
TelithromycinTelithromycin may reduce clearance of Digitoxin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Digitoxin if Telithromycin is initiated, discontinued or dose changed.
VerapamilVerapamil may increase the serum concentration of Digitoxin by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of Digitoxin if Verpamail is initiated, discontinued or dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of digitoxin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of digitoxin if voriconazole is initiated, discontinued or dose changed.
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.

1. Sodium/potassium-transporting ATPase subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium/potassium-transporting ATPase subunit alpha-1 P05023 Details

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
  2. Marcus FI, Ryan JN, Stafford MG: The reactivity of derivatives of digoxin and digitoxin as measured by the Na-K-atpase displacement assay and by radioimmunoassay. J Lab Clin Med. 1975 Apr;85(4):610-20. Pubmed
  3. Prignitz R, Frohlich D, Hoffmeister G: [Influence of roentgen rays on electrolyte changes and metabolism of the myocardium. VII. Radiation-induced inhibition of the sodium- and potassium—activated microscomal-trasport ATPase] Strahlentherapie. 1976 Apr;151(4):356-65. Pubmed
  4. Bluschke V, Bonn R, Greeff K: Increase in the (Na+ + K+)-ATPase activity in heart muscle after chronic treatment with digitoxin or potassium deficient diet. Eur J Pharmacol. 1976 May;37(1):189-91. Pubmed
  5. Fricke U: [New aspects on the mode of action of cardiac glycosides] Fortschr Med. 1976 Nov 11;94(32):1037-45. Pubmed
  6. Hauck C, Potter T, Bartz M, Wittwer T, Wahlers T, Mehlhorn U, Scheiner-Bobis G, McDonough AA, Bloch W, Schwinger RH, Muller-Ehmsen J: Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase alpha1beta1, alpha2beta1 and alpha3beta1. Eur J Pharmacol. 2009 Nov 10;622(1-3):7-14. Epub 2009 Sep 12. Pubmed

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

2. Cholesterol side-chain cleavage enzyme, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cholesterol side-chain cleavage enzyme, mitochondrial P05108 Details

References:

  1. Wang SW, Lin H, Hwang JJ, Wang PS: Inhibition of testosterone secretion by digitoxin in rat testicular interstitial cells. J Cell Biochem. 1999 Jul 1;74(1):74-80. Pubmed

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Hage DS, Sengupta A: Characterisation of the binding of digitoxin and acetyldigitoxin to human serum albumin by high-performance affinity chromatography. J Chromatogr B Biomed Sci Appl. 1999 Mar 5;724(1):91-100. Pubmed
  2. Dasgupta A, Vega AE, Wells A, Datta P: Sensitive methods for determination of free digitoxin concentration using digitoxin immunoassays: demonstration of elevated free digitoxin concentration caused by digitoxin-phenytoin interaction by applying these new techniques. Ther Drug Monit. 1999 Dec;21(6):625-30. Pubmed
  3. Datta P, Dasgupta A: Interactions between drugs and Asian medicine: displacement of digitoxin from protein binding site by bufalin, the constituent of Chinese medicines Chan Su and Lu-Shen-Wan. Ther Drug Monit. 2000 Apr;22(2):155-9. Pubmed
  4. Dasgupta A, Paul A, Wells A: Uremic sera contain inhibitors that block digitoxin-valproic acid interaction. Am J Med Sci. 2001 Oct;322(4):204-8. Pubmed

1. Solute carrier organic anion transporter family member 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

References:

  1. Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. Pubmed

2. Solute carrier organic anion transporter family member 4C1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 4C1 Q6ZQN7 Details

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

3. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Pauli-Magnus C, Murdter T, Godel A, Mettang T, Eichelbaum M, Klotz U, Fromm MF: P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin. Naunyn Schmiedebergs Arch Pharmacol. 2001 Mar;363(3):337-43. Pubmed

Comments
Drug created on July 08, 2007 11:03 / Updated on September 16, 2013 17:14