Digoxin

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C41H64O14
Molecular Weight	780.9385
Optical Activity	UNSPECIFIED
Defined Stereocenters	21 / 21
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(C[C@H](O)[C@H](O[C@@]2([H])C[C@H](O)[C@H](O[C@@]3([H])C[C@H](O)[C@H](O)[C@@H](C)O3)[C@@H](C)O2)[C@@H](C)O1)O[C@H]4CC[C@@]5(C)[C@]([H])(CC[C@]6([H])[C@]5([H])C[C@@H](O)[C@]7(C)[C@H](CC[C@]67O)C8=CC(=O)OC8)C4

InChI

InChIKey=LTMHDMANZUZIPE-PUGKRICDSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00390
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/digoxin.html

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. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Y79 1 Target ID: CHEMBL613820 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26176875	Inhibitor 8297	0.1 µM [IC50]
Glucose-6-phosphate 1-dehydrogenase 12 Target ID: P05370 Gene ID: 24377.0 Gene Symbol: G6pdx Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26820767	Inhibitor 8297	0.09 mM [IC50]
6-phosphogluconate dehydrogenase, decarboxylating 29 Target ID: P85968 Gene ID: 1.00360176E8 Gene Symbol: Pgd Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26820767	Inhibitor 8297	0.14 mM [IC50]
Glutathione reductase 11 Target ID: CHEMBL3286088 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26820767	Inhibitor 8297	0.22 mM [IC50]
Sodium/potassium-transporting ATPase 39 Target ID: CHEMBL2095186 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12904068	Inhibitor 8297	0.4 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Heart failure 103 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/009330s030lbl.pdf	Primary		Approved 8429	LANOXIN Approved Use LANOXIN is a cardiac glycoside indicated for: Treatment of mild to moderate heart failure in adults. Increasing myocardial contractility in pediatric patients with heart failure. Control of resting ventricular rate in adults with chronic atrial fibrillation. Launch Date -5.05007997E11
Chronic atrial fibrillation 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/009330s030lbl.pdf	Primary		Approved 8429	LANOXIN Approved Use LANOXIN is a cardiac glycoside indicated for: Treatment of mild to moderate heart failure in adults. Increasing myocardial contractility in pediatric patients with heart failure. Control of resting ventricular rate in adults with chronic atrial fibrillation. Launch Date -5.05007997E11

C_max

Value	Dose	Co-administered	Analyte	Population
1.32 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18823299	0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered:		DIGOXIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
12.5 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18823299	0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered:		DIGOXIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
42 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020405s013lbl.pdf	unknown, intravenous		DIGOXIN unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
75% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020405s013lbl.pdf	unknown, intravenous		DIGOXIN unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
22.5 mg single, oral Overdose Dose: 22.5 mg Route: oral Route: single Dose: 22.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2592582 Page: p.901, 902	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2592582 Page: p.901, 902	Disc. AE: Vomiting, Lethargy... AEs leading to discontinuation/dose reduction: Vomiting Lethargy Tachycardia Sources: https://pubmed.ncbi.nlm.nih.gov/2592582 Page: p.901, 902
25 mg single, oral Overdose Dose: 25 mg Route: oral Route: single Dose: 25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393	healthy, 26 n = 1 Health Status: healthy Age Group: 26 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393	Disc. AE: Blurred vision, Sinus bradycardia... AEs leading to discontinuation/dose reduction: Blurred vision Sinus bradycardia Electrocardiogram ST segment depression Heart block Ventricular tachycardia Ventricular fibrillation Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393
18 mg single, oral Overdose Dose: 18 mg Route: oral Route: single Dose: 18 mg Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100	healthy, 41 n = 1 Health Status: healthy Age Group: 41 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100	Disc. AE: Hyperkalemia, Nausea... AEs leading to discontinuation/dose reduction: Hyperkalemia Nausea Vomiting Lethargy Atrioventricular block Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100

AEs

AE	Significance	Dose	Population
Lethargy	Disc. AE	22.5 mg single, oral Overdose Dose: 22.5 mg Route: oral Route: single Dose: 22.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2592582 Page: p.901, 902	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2592582 Page: p.901, 902
Tachycardia	Disc. AE	22.5 mg single, oral Overdose Dose: 22.5 mg Route: oral Route: single Dose: 22.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2592582 Page: p.901, 902	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2592582 Page: p.901, 902
Vomiting	Disc. AE	22.5 mg single, oral Overdose Dose: 22.5 mg Route: oral Route: single Dose: 22.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/2592582 Page: p.901, 902	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2592582 Page: p.901, 902
Blurred vision	Disc. AE	25 mg single, oral Overdose Dose: 25 mg Route: oral Route: single Dose: 25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393	healthy, 26 n = 1 Health Status: healthy Age Group: 26 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393
Electrocardiogram ST segment depression	Disc. AE	25 mg single, oral Overdose Dose: 25 mg Route: oral Route: single Dose: 25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393	healthy, 26 n = 1 Health Status: healthy Age Group: 26 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393
Heart block	Disc. AE	25 mg single, oral Overdose Dose: 25 mg Route: oral Route: single Dose: 25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393	healthy, 26 n = 1 Health Status: healthy Age Group: 26 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393
Sinus bradycardia	Disc. AE	25 mg single, oral Overdose Dose: 25 mg Route: oral Route: single Dose: 25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393	healthy, 26 n = 1 Health Status: healthy Age Group: 26 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393
Ventricular fibrillation	Disc. AE	25 mg single, oral Overdose Dose: 25 mg Route: oral Route: single Dose: 25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393	healthy, 26 n = 1 Health Status: healthy Age Group: 26 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393
Ventricular tachycardia	Disc. AE	25 mg single, oral Overdose Dose: 25 mg Route: oral Route: single Dose: 25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393	healthy, 26 n = 1 Health Status: healthy Age Group: 26 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6409318 Page: p.393
Atrioventricular block	Disc. AE	18 mg single, oral Overdose Dose: 18 mg Route: oral Route: single Dose: 18 mg Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100	healthy, 41 n = 1 Health Status: healthy Age Group: 41 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100
Hyperkalemia	Disc. AE	18 mg single, oral Overdose Dose: 18 mg Route: oral Route: single Dose: 18 mg Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100	healthy, 41 n = 1 Health Status: healthy Age Group: 41 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100
Lethargy	Disc. AE	18 mg single, oral Overdose Dose: 18 mg Route: oral Route: single Dose: 18 mg Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100	healthy, 41 n = 1 Health Status: healthy Age Group: 41 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100
Nausea	Disc. AE	18 mg single, oral Overdose Dose: 18 mg Route: oral Route: single Dose: 18 mg Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100	healthy, 41 n = 1 Health Status: healthy Age Group: 41 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100
Vomiting	Disc. AE	18 mg single, oral Overdose Dose: 18 mg Route: oral Route: single Dose: 18 mg Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100	healthy, 41 n = 1 Health Status: healthy Age Group: 41 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/490791 Page: p.2100

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 788 OATP1B3 706	CYP450 65 P-gp 1537 OATP1B3 350

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20102298/	yes [IC50 1 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20102298/	yes [IC50 7.9 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP450 65	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020405s015lbl.pdf#page=23 Page: 23.0	no
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11159893/	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020405s015lbl.pdf#page=10 Page: 10.0	yes	yes (co-administration study) Comment: Many drug drug interactions. See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020405s015lbl.pdf#page=11 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020405s015lbl.pdf#page=10 Page: 10.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/17095614/ Page: 3.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4551	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4551
MolPort	MolPort-002-536-760	https://www.molport.com/shop/molecule-link/MolPort-002-536-760
ZINC	ZINC000242548690	http://zinc15.docking.org/substances/ZINC000242548690
eMolecules	4849372	https://www.emolecules.com/cgi-bin/more?vid=4849372
eMolecules	502132	https://www.emolecules.com/cgi-bin/more?vid=502132

PubMed

Title	Date	PubMed
[Digitalis intoxication: specifity and significance of cardiac and extracardiac symptoms. part I: Patients with digitalis-induced arrhythmias (author's transl)].	1977 Mar	857452
Verapamil and digoxin: interactions in the rat.	1983 Dec	6665298
Drug-induced gynecomastia.	1993 Jan-Feb	8094898
26-10 Fab-digoxin complex: affinity and specificity due to surface complementarity.	1993 Nov 1	8234291
Isolation and characterization of human monoclonal antibodies to digoxin.	1999 Aug 15	10438974
Fab antibody fragments: some applications in clinical toxicology.	2004	15554746
No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract.	2005 Apr	15856409
Digoxin suppresses HIV-1 replication by altering viral RNA processing.	2013 Mar	23555254

Patents

Sample Use Guides

In Vivo Use Guide

Tablets: Initial: 500 to 750 mcg usually produces a detectable effect in 0.5 to 2 hours with a maximal effect in 2 to 6 hours. Additional doses of 125 to 375 mcg may be given at 6 to 8 hour intervals until clinical evidence of an adequate effect is noted. The usual amount of digoxin tablets that a 70 kg patient requires to achieve 8 to 12 mcg/kg peak body stores is 750 to 1250 mcg. Injection: Initial: 400 to 600 mcg of digoxin intravenously usually produces a detectable effect in 5 to 30 minutes with a maximal effect in 1 to 4 hours. Additional doses of 100 to 300 mcg may be given cautiously at 6 to 8 hour intervals until clinical evidence of an adequate effect is noted. The usual amount of digoxin injection that a 70 kg patient requires to achieve 8 to 12 mcg/kg peak body stores is 600 to 1000 mcg.

Route of Administration: Other

In Vitro Use Guide

Digoxin was effective against B. mandrillaris at 250uM

Name

Type

Language

Digoxin

Official Name

English

DYNAMOS

Common Name

English

DIGOXIN [IARC]

Common Name

English

STILLACOR-

Common Name

English

LANOCARDIN

Common Name

English

DIGOXIN [WHO-IP]

Common Name

English

DIGOXIN [MI]

Common Name

English

Digoxin [WHO-DD]

Common Name

English

TOLOXIN

Common Name

English

MAPLUXIN

Common Name

English

DIGOXIN [VANDF]

Common Name

English

DIGOXIN [EP MONOGRAPH]

Common Name

English

DIGOXIN [HSDB]

Common Name

English

3.BETA.-((O-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-O-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL)OXY)-12.BETA.,14-DIHYDROXY-5.BETA.-CARD-20(22)-ENOLIDE

Common Name

English

DIGOXINUM [WHO-IP LATIN]

Common Name

English

NATIGOXIN

Common Name

English

digoxin [INN]

Common Name

English

DIGOXIN [USP-RS]

Common Name

English

DIGOXIN [MART.]

Common Name

English

DIGOXIN [JAN]

Common Name

English

DIGOXIN [USP MONOGRAPH]

Common Name

English

VANOXIN

Common Name

English

CARD-20(22)-ENOLIDE, 3-((O-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-O-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL-(1->4)-2,6-DIDEOXY-.BETA.-D-RIBO-HEXOPYRANOSYL)OXY)-12,14-DIHYDROXY-,(3.BETA.,5.BETA.,12.BETA.)-

Common Name

English

NSC-95100

Code

English

DIGOXIN [ORANGE BOOK]

Common Name

English

LANOXIN

Brand Name

English

ROUGOXIN

Common Name

English

FARGOXIN

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175568