Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0498)
Drug Name
Digoxin
Synonyms
Digacin; Digosin; Digossina; Digoxin Nativelle; Digoxin Pediatric; Digoxina; Digoxine; Digoxinum; Dilanacin; Dynamos; Eudigox; Cardiogoxin; Davoxin; Hemigoxine Nativelle; Homolle's digitalin; Lanacordin; Lanacrist; Lanicor; Lanoxicaps; Lanoxin; Lanoxin PG; Lenoxin; Mapluxin; Neo-Lanicor; Rougoxin; SK-Digoxin; Vanoxin; digoxin; 12beta-Hydroxydigitoxin; 20830-75-5; CHEBI:4551; MFCD00003674; MLS000069819; SMR000059217; UNII-73K4184T59
Indication Cardiac arrhythmia [ICD11: BC65] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 780.9 Topological Polar Surface Area 203
Heavy Atom Count 55 Rotatable Bond Count 7
Hydrogen Bond Donor Count 6 Hydrogen Bond Acceptor Count 14
Cross-matching ID
PubChem CID
2724385
PubChem SID
9171 ; 3139699 ; 7847364 ; 7979083 ; 8787891 ; 10321270 ; 11466465 ; 11467585 ; 11486129 ; 11533002 ; 14840467 ; 16531631 ; 17389540 ; 24893992 ; 24894045 ; 25664046 ; 26752810 ; 29204039 ; 30082596 ; 46508524 ; 47277036 ; 47350829 ; 47500941 ; 47871144 ; 48415894 ; 48425070 ; 48493824 ; 49698492 ; 49718191 ; 50105460 ; 50105461 ; 56313674 ; 56422204 ; 57287890 ; 57409429 ; 57654114 ; 79412392 ; 85788562 ; 87568294 ; 90481132 ; 92125420 ; 92298240 ; 92729949 ; 93167166 ; 99431517 ; 103707689 ; 103913751 ; 111366106 ; 117393920 ; 121363091
ChEBI ID
CHEBI:4551
CAS Number
20830-75-5
TTD Drug ID
D02OZE
Formula
C41H64O14
Canonical SMILES
CC1C(C(CC(O1)OC2C(OC(CC2O)OC3C(OC(CC3O)OC4CCC5(C(C4)CCC6C5CC(C7(C6(CCC7C8=CC(=O)OC8)O)C)O)C)C)C)O)O
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
InChIKey
LTMHDMANZUZIPE-PUGKRICDSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
Digoxigenin-bisdigitoxoside DM000084
92999
Oxidation - Cleavage 1 [6]
Dihydrodigoxin DM000088
92217
Reduction - Reduction 1 [2] , [7]
Digoxigenin-monodigitoxoside DM000085
93001
Oxidation - Cleavage 2 [6]
Dihydrodigoxigenin-bisdigitoxoside DM000089 N. A. Oxidation - Cleavage 2 [7]
DG1 glucuronidation DM000087 N. A. Conjugation - Glucuronidation 3 [8]
Digoxigenin DM000086
15478
Oxidation - Cleavage 3 [7]
Dihydrodigoxigenin-monodigitoxoside DM000090 N. A. Oxidation - Cleavage 3 [7]
Digitoxigenin sulfated cardioinactive compound DM000079 N. A. Conjugation - Conjugation 4 [7]
Dihydrodigoxigenin DM000091 N. A. Oxidation - Cleavage 4 [7]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000855 Digoxin Digoxigenin-bisdigitoxoside Oxidation - Cleavage CYP3A4 [6]
MR000856 Digoxin Dihydrodigoxin Reduction - Reduction Cgr1 ... [2], [7]
MR000848 Digoxigenin-bisdigitoxoside Digoxigenin-monodigitoxoside Oxidation - Cleavage CYP3A4 [6]
MR000852 Dihydrodigoxin Dihydrodigoxigenin-bisdigitoxoside Oxidation - Cleavage Unclear [7]
MR000849 Digoxigenin-monodigitoxoside Digoxigenin Oxidation - Cleavage Unclear [7]
MR000850 Digoxigenin-monodigitoxoside DG1 glucuronidation Conjugation - Glucuronidation UGT [8]
MR000853 Dihydrodigoxigenin-bisdigitoxoside Dihydrodigoxigenin-monodigitoxoside Oxidation - Cleavage Unclear [7]
MR000851 Digoxigenin Digitoxigenin sulfated cardioinactive compound Conjugation - Conjugation Unclear [7]
MR000854 Dihydrodigoxigenin-monodigitoxoside Dihydrodigoxigenin Oxidation - Cleavage Unclear [7]
⏷ Show the Full List of 9 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cardiac glycoside reductase 1 (cgr1) DME1035 Eggerthella lenta
CGR1_EGGLE
1.3.2.-
[2]
Cardiac glycoside reductase 2 (cgr2) DME1036 Eggerthella lenta
CGR2_EGGLE
1.3.2.-
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1254 Bacteroides thetaiotaomicron Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1364 Bacteroides coprophilus Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1365 Bacteroides dorei Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1366 Bacteroides eggerthii Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1376 Bacteroides ovatus Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1379 Bacteroides stercoris Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1384 Bacteroides vulgatus Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1385 Bacteroides xylanisolvens Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1402 Clostridium botulinum Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1415 Eggerthella lenta Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1444 Odoribacter splanchnicus Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1446 Parabacteroides johnsonii Not Available Not Available [4]
Unclear metabolic mechanism (DME-unclear) DME1447 Parabacteroides merdae Not Available Not Available [4]
⏷ Show the Full List of 19  DME(s)
References
1 Digoxin was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Mechanistic insight into digoxin inactivation by Eggerthella lenta augments our understanding of its pharmacokinetics. Gut Microbes. 2014 Mar-Apr;5(2):233-8.
3 Omeprazole-associated digoxin toxicity. South Med J. 2007 Apr;100(4):400-2.
4 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
5 Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora. Gut. 1989 Jul;30(7):971-7.
6 Metabolism of digoxin and digoxigenin digitoxosides in rat liver microsomes: involvement of cytochrome P4503A Xenobiotica. 1999 Feb;29(2):171-85. doi: 10.1080/004982599238722.
7 American Society of Health System Pharmacists; AHFS Drug Information 2010. Bethesda, MD. (2010), p. 2511
8 Metabolism of digoxin, digoxigenin digitoxosides and digoxigenin in human hepatocytes and liver microsomes Fundam Clin Pharmacol. 1991;5(7):567-82. doi: 10.1111/j.1472-8206.1991.tb00746.x.

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