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Drug

D0884 | digoxin

Molecular Formula C41H64O14
Molecular Weight 780.9
Structure
State solid
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.[L6775] One pharmacokinetic study measured the mean body clearance of intravenous digoxin to be 88 ± 44ml/min/l.73 m².[A178324] 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.[A178318]
Volume of distribution This drug is widely distributed in the body, and is known to cross the blood-brain barrier and the placenta.[L6775,A178228] The apparent volume of distribution of digoxin is 475-500 L.[L6775] A large portion of digoxin is distributed in the skeletal muscle followed by the heart and kidneys.[A178228] It is important to note that the elderly population, generally having a decreased muscle mass, may show a lower volume of digoxin distribution.[L6775]
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.[A178228] 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.[L6775]
Protein binding Digoxin protein binding is approximately 25%.[L6775] It is mainly bound to albumin.[A178228]
Half life Digoxin has a half-life of 1.5-2 days in healthy subjects.[L6775] 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.[L6775]
Absorption Digoxin is approximately 70-80% absorbed in the first part of the small bowel.[A178228] The bioavailability of an oral dose varies from 50-90%, however, oral gelatinized capsules of digoxin are reported to have a bioavailability of 100%.[A178252] 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.[A178369] 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.[A178369] 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.[L6274] **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.[L6775] **A note on malabsorption** Patients with malabsorption due to a variety of causes may have a decreased ability to absorb digoxin.[L6775] 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.[L6775]

C

C01AA05 Digoxin


[C01AA] Digitalis glycosides


[C01A] CARDIAC GLYCOSIDES


[C01] CARDIAC THERAPY


[C] Cardiovascular system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
MEMBRANE POTENTIAL 0.52±0.09 human qHTS-HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 0.13 human HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL rat hepatocytes MMP assay Negative IC50 163

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 119 companies from 14 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H300+H330 (31.93%): Fatal if swallowed or if inhaled [Danger Acute toxicity, oral


acute toxicity, inhalation]


H300 (85.71%): Fatal if swallowed [Danger Acute toxicity, oral]


H319 (51.26%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H330 (81.51%): Fatal if inhaled [Danger Acute toxicity, inhalation]


H331 (10.08%): Toxic if inhaled [Danger Acute toxicity, inhalation]


H372 (43.7%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]


H400 (56.3%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P260, P261, P264, P270, P271, P273, P280, P284, P301+P310, P304+P340, P305+P351+P338, P310, P311, P314, P320, P321, P330, P337+P313, P391, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

H300: Fatal if swallowed [Danger Acute toxicity, oral]


H330: Fatal if inhaled [Danger Acute toxicity, inhalation]


 P260, P264, P270, P271, P284, P301+P310, P304+P340, P310, P320, P321, P330, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)


  • (3beta,5beta,12beta)-3-((O-2,6-Dideoxy-beta-D-ribo-hexapyranosyl-(1-4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1-4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl)oxy)-12,14-dihydroxycard-20(22)-enolide (3beta,5beta,12beta)-3-{[2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1->4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl]oxy}-12,14-dihydroxycard-20(22)-enolide 0B9662A7-264E-4ACD-94B2-9E1138C0CA5A
    12bet.-Hydroxydigitoxin 12beta-Hydroxydigitoxin 20830-75-5
    3-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-10,13-dimethyl-3-[(2R,4S,5S,6R)-6-methyl-5-[(2S,4S,5S,6R)-6-methyl-5-[(2S,4S,5S,6R)-6-methyl-4,5-bis(oxidanyl)oxan-2-yl]oxy-4-oxidanyl-oxan-2-yl]oxy-4-oxidanyl-oxan-2-yl]oxy-12,14-bis(oxidanyl)-1,2,3,4,5,6,7,8,9,11,12, 3-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(2R,4S,5S,6R)-5-[(2S,4S,5S,6R)-5-[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-4-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-4-hydroxy-6-methyl-tetrahydropyran-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]-2H-furan-5-one 3-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(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-12,14-dihydr
    3-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(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-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]-2H-furan-5-one 3-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[[(2R,4S,5S,6R)-5-[[(2S,4S,5S,6R)-5-[[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyl-2-oxanyl]oxy]-4-hydroxy-6-methyl-2-oxanyl]oxy]-4-hydroxy-6-methyl-2-oxanyl]oxy]-12,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16, 3b0w
    3beta,12beta,14-Trihydroxy-5beta,14beta-card-20(22)-enolid-3-tridigitoxosid 3beta-((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)-12beta,14-dihydroxy-5beta-card-20(22)-enolide 4-((1S,2S,5S,11S,15S,7R,10R,14R,16R)-5-{5-[5-((2S,4S,5S,6R)-4,5-dihydroxy-6-me thyl(2H-3,4,5,6-tetrahydropyran-2-yloxy))(4S,5S,2R,6R)-4-hydroxy-6-methyl(2H-3 ,4,5,6-tetrahydropyran-2-yloxy)](4S,5S,2R,
    4-((1S,2S,5S,11S,15S,7R,10R,14R,16R)-5-{5-[5-((2S,4S,5S,6R)-4,5-dihydroxy-6-me thyl(2H-3,4,5,6-tetrahydropyran-2-yloxy))(4S,5S,2R,6R)-4-hydroxy-6-methyl(2H-3 ,4,5,6-tetrahydropyran-2-yloxy)](4S,5S,2R,6R)-4-hydroxy-6-methyl(2H-3,4,5,6-te trahydropyran-2-yl 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[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-yl]-2,5-dihydrofuran-2-one 5-18-04-00381 (Beilstein Handbook Reference)
    6R)-4-hydroxy-6-methyl(2H-3,4,5,6-te trahydropyran-2-yloxy)}-11,16-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0<2,7>.0 <11,15>]heptadec-14-yl)-5-hydrofuran-2-one 73K4184T59 830D755
    A814956 AKOS015895113 AKOS024283494
    AS-13281 Acygoxin B7684
    BDBM46355 BIDD:PXR0148 BPBio1_000500
    BRD-K23478508-001-03-7 BRN 0077011 BSPBio_000454
    C-23516 C06956 C41H64O14
    CAS-20830-75-5 CC-26802 CCG-220437
    CHEBI:4551 CHEMBL1751 CS-4571
    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-, (3beta,5beta,12beta)- 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-, (3beta,5beta,12beta)- Card-20(22)-enolide, 3-((O-2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1.fwdarw.4)-O-2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1.fwdarw.4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl)oxy)-12,14-dihydroxy-, (3beta,5beta,12beta)-
    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.)-; Cardigox Cardiogoxin
    Cardioxin Certified Reference Material Chloroformic digitalin
    Coragoxine Cordioxil D00298
    D1828 DB00390 DSSTox_CID_2934
    DSSTox_GSID_22934 DSSTox_RID_76794 DTXSID5022934
    Davoxin Digacin Digitek
    Digoksyna Digoksyna [Polish] Digomal
    Digon Digonix Digos
    Digosin Digossina Digossina [DCIT]
    Digoxigenin-tridigitoxosid Digoxigenin-tridigitoxosid [German] Digoxin (JP17/USP)
    Digoxin 1.0 mg/ml in Methanol Digoxin Nativelle Digoxin Pediatric
    Digoxin [USP:INN:BAN:JAN] Digoxin for peak identification, European Pharmacopoeia (EP) Reference Standard Digoxin solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material
    Digoxin, 95% Digoxin, European Pharmacopoeia (EP) Reference Standard Digoxin, Pharmaceutical Secondary Standard
    Digoxin, United States Pharmacopeia (USP) Reference Standard Digoxin, analytical standard Digoxin, certified reference material, TraceCERT(R)
    Digoxin-Sandoz Digoxin-Zori Digoxina
    Digoxina [INN-Spanish] Digoxina-Sandoz Digoxine
    Digoxine Navtivelle Digoxinum Digoxinum [INN-Latin]
    Dilanacin Dimecip Dixina
    Dokim Dynamos EINECS 244-068-1
    Epitope ID:122964 Eudigox Fargoxin
    GTPL4725 GTPL4726 Grexin
    H797 HMS1569G16 HMS2096G16
    HMS2232G20 HMS3713G16 HSDB 214
    HY-B1049 Hemigoxine Nativelle Homolle's digitalin
    J-013666 J10027 LANOXIN PEDIATRIC
    LTMHDMANZUZIPE-PUGKRICDSA-N Lanacordin Lanacrist
    Lanicor Lanikor Lanorale
    Lanoxicaps Lanoxicaps (TN) Lanoxin
    Lanoxin (TN) Lanoxin PG Lenoxicaps
    Lenoxin Lifusin MCULE-8165628529
    MFCD00003674 MLS000069819 MLS001055371
    MLS001076495 Mapluxin NCGC00090797-01
    NCGC00090797-02 NCGC00090797-03 NCGC00090797-04
    NCGC00090797-05 NCGC00090797-06 NCGC00090797-07
    NCGC00090797-09 NCGC00090797-15 NCGC00257022-01
    NCGC00259227-01 NSC 95100 NSC-95100
    Natigoxin Neo-Lanicor Neodioxanin
    Novodigal [inj.] Opera_ID_1134 Prestwick0_000437
    Prestwick1_000437 Prestwick2_000437 Prestwick3_000437
    Prestwick_170 Purgoxin Q422222
    REGID_for_CID_2724385 Rougoxin SCHEMBL20506
    SK-Digoxin SMR000059217 SMR000653537
    SPBio_002393 SR-01000721866 SR-01000721866-3
    SR-01000721866-4 ST069334 Saroxin
    Tox21_111025 Tox21_201678 Tox21_303050
    UNII-73K4184T59 Vanoxin ZINC242548690
    ZX-AFC001295 [3H]-digoxin [3H]digoxin
    cid_2724385 digoxin oxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
    s4290

    DrugBank Name digoxin
    DrugBank DB00390
    CAS Number 20830-75-5
    PubChem Compound 2724385
    KEGG Compound ID C06956
    KEGG Drug D00298
    ChEBI 4551
    PharmGKB PA449319