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Identification
NameDigoxin
Accession NumberDB00390  (APRD00098)
Typesmall molecule
Groupsapproved
Description

A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)

Structure
Thumb
Synonyms
SynonymLanguageCode
12β-hydroxydigitoxinNot AvailableNot Available
4-[(3S,5R,8R,9S,10S,12R,13S,14S)-3-[(2S,4S,5R,6R)-5-[(2S,4S,5R,6R)-5-[(2S,4S,5R,6R)-4,5-dihydroxy-6-methyl-oxan-2-yl]oxy-4-hydroxy-6-methyl-oxan-2-yl]oxy-4-hydroxy-6-methyl-oxan-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]-5H-furan-2-oneNot AvailableIUPAC
DigazolanNot AvailableIS
DigossinaNot AvailableDCIT
DigoxinNot AvailableJAN, BAN, BP 2011, JP XV, Ph. Eur. 7, Ph. Int. 4, USP 34
DigoxinaSpanishINN
DigoxineFrenchINN
DigoxinumLatinINN
LanadicorNot AvailableIS
SaltsNot Available
Brand names
NameCompany
AgoxinAristopharma
CardiacinCenter
CardiogoxinMedipharma
CardioxinOboi
CardoxinNot Available
CeloxinCelon
CentoxinOpsonin
Digacinmibe
DigitekMylan
Digocard-GKlonal
DigoxinaGlaxoSmithKline
EudigoxTeofarma
LanacordinKern
LanacristNot Available
LanicorRoche
LanoxicapsNot Available
LanoxinGlaxoSmithKline
LenoxinGlaxoSmithKline
Brand mixturesNot Available
Categories
CAS number20830-75-5
WeightAverage: 780.9385
Monoisotopic: 780.429606756
Chemical FormulaC41H64O14
InChI KeyInChIKey=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[8.7.0.0^{2,7}.0^{11,15}]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
Mass SpecNot Available
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; 12-hydroxy-steroid; 14-hydroxy-steroid; trisaccharide; glycosyl compound; o-glycosyl compound; cyclohexanol; 2-furanone; saccharide; oxane; tertiary alcohol; cyclic alcohol; dihydrofuran; secondary alcohol; carboxylic acid ester; 1,2-diol; 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.
PharmacodynamicsDigoxin, 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.
Mechanism of actionDigoxin 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.
AbsorptionAbsorption of digoxin from the elixir pediatric formulation has been demonstrated to be 70% to 85% complete (90% to 100% from the capsules, and 60% to 80% for tablets).
Volume of distributionNot Available
Protein binding25%
Metabolism

Hepatic (but not dependent upon the cytochrome P-450 system). The end metabolites, which include 3 b-digoxigenin, 3-keto-digoxigenin, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation.

SubstrateEnzymesProduct
Digoxin
    3 b-digoxigeninDetails
    Digoxin
      3-keto-digoxigeninDetails
      Route of eliminationFollowing intravenous administration to healthy volunteers, 50% to 70% of a digoxin dose is excreted unchanged in the urine.
      Half life3.5 to 5 days
      ClearanceNot Available
      ToxicityToxicity includes ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block. LD50 = 7.8 mg/kg (orally in mice).
      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 + 0.941
      Blood Brain Barrier - 0.7241
      Caco-2 permeable - 0.8957
      P-glycoprotein substrate Substrate 0.8586
      P-glycoprotein inhibitor I Non-inhibitor 0.5325
      P-glycoprotein inhibitor II Non-inhibitor 0.6209
      Renal organic cation transporter Non-inhibitor 0.8621
      CYP450 2C9 substrate Non-substrate 0.855
      CYP450 2D6 substrate Non-substrate 0.9116
      CYP450 3A4 substrate Substrate 0.7366
      CYP450 1A2 substrate Non-inhibitor 0.9261
      CYP450 2C9 substrate Non-inhibitor 0.9196
      CYP450 2D6 substrate Non-inhibitor 0.9359
      CYP450 2C19 substrate Non-inhibitor 0.9385
      CYP450 3A4 substrate Non-inhibitor 0.9279
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9279
      Ames test Non AMES toxic 0.9233
      Carcinogenicity Non-carcinogens 0.9668
      Biodegradation Not ready biodegradable 0.9555
      Rat acute toxicity 4.4721 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.9818
      hERG inhibition (predictor II) Inhibitor 0.8051
      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
      Dosage forms
      FormRouteStrength
      LiquidIntravenous
      Powder, for solutionIntravenous
      SolutionOral
      TabletOral
      Prices
      Unit descriptionCostUnit
      Digibind 38 mg vial727.91USDvial
      Digifab 40 mg vial615.6USDvial
      Digoxin powder450.28USDg
      Digoxin 0.05 mg/ml Solution 60ml Bottle36.99USDbottle
      Lanoxin ped 0.1 mg/ml ampul6.91USDml
      Digoxin Pediatric 0.05 mg/ml6.79USDml
      Digoxin 0.25 mg/ml2.91USDml
      Lanoxin 0.25 mg/ml ampul1.44USDml
      Lanoxin 0.125 mg tablet0.73USDtablet
      Lanoxin 0.25 mg tablet0.66USDtablet
      Digoxin 0.125 mg tablet0.64USDtablet
      Digoxin 0.25 mg tablet0.62USDtablet
      Digoxin 0.25 mg/ml ampul0.61USDml
      Lanoxin Pediatric 0.05 mg/ml Elixir0.41USDml
      Lanoxicaps 0.1 mg capsule0.4USDcapsule
      Lanoxin 125 mcg tablet0.3USDtablet
      Lanoxin 250 mcg tablet0.3USDtablet
      Digitek 125 mcg tablet0.28USDtablet
      Digitek 250 mcg tablet0.28USDtablet
      Lanoxicaps 0.05 mg capsule0.28USDcapsule
      Toloxin 0.0625 mg Tablet0.27USDtablet
      Toloxin 0.125 mg Tablet0.27USDtablet
      Toloxin 0.25 mg Tablet0.27USDtablet
      Digoxin 125 mcg tablet0.22USDtablet
      Digoxin 250 mcg tablet0.22USDtablet
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      PatentsNot Available
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point217-221Stoll, A .and Kreis, W.; US.Patent 2,776,963; January 8,1957;assigned to Sandoz, AG, Switzerland.
      water solubility64.8 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
      logP1.26SANGSTER (1993)
      Predicted Properties
      PropertyValueSource
      water solubility1.27e-01 g/lALOGPS
      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 area203.06ChemAxon
      rotatable bond count7ChemAxon
      refractivity193.23ChemAxon
      polarizability84.8ChemAxon
      number of rings8ChemAxon
      bioavailability0ChemAxon
      rule of fiveNoChemAxon
      Ghose filterNoChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleYesChemAxon
      Spectra
      SpectraNot Available
      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 Reference
      1. Thompson DF, Carter JR: Drug-induced gynecomastia. Pharmacotherapy. 1993 Jan-Feb;13(1):37-45. Pubmed
      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
      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
      4. Flanagan RJ, Jones AL: Fab antibody fragments: some applications in clinical toxicology. Drug Saf. 2004;27(14):1115-33. Pubmed
      External Links
      ResourceLink
      KEGG DrugD00298
      KEGG CompoundC06956
      BindingDB50115625
      ChEBI4551
      ChEMBLCHEMBL1751
      Therapeutic Targets DatabaseDAP000744
      PharmGKBPA449319
      Drug Product Database2242323
      RxListhttp://www.rxlist.com/cgi/generic/dig.htm
      Drugs.comhttp://www.drugs.com/digoxin.html
      WikipediaDigoxin
      ATC CodesC01AA02C01AA05C01AA08
      AHFS Codes
      • 24:04.08
      • 80:04.00
      PDB EntriesNot Available
      FDA labelshow(563 KB)
      MSDSshow(74.6 KB)
      Interactions
      Drug Interactions
      Drug
      AcarboseAcarbose may decrease the serum levels of digoin. It is thought that acarbose reduces digoin absorption. Monitor for changes in digoxin serum levels and therapeutic and adverse effects if acarbose is initiated, discontinued or dose changed.
      AlprazolamThe benzodiazepine, alprazolam, may increase the effect of digoxin.
      AmiodaroneAmiodarone may increase the effect of digoxin.
      BendroflumethiazidePossible electrolyte variations and arrhythmias
      BenzthiazidePossible electrolyte variations and arrhythmias
      BleomycinThe antineoplasic agent decreases the effect of digoxin
      BosutinibBosutinib is a substrate and inhibitor of p-glycoprotein (p-gp) and may increase levels of other p-gp substrates.
      BumetanidePossible electrolyte variations and arrhythmias
      CanagliflozinWhen coadministered with 300 mg canagliflozin, the AUC and mean peak drug concentration of digoxin increased. Monitor concomitant therapy closely.
      CarmustineThe antineoplasic agent decreases the effect of digoxin
      CarvedilolCarvedilol may increase the serum levels and effect of digoxin.
      ChlorothiazidePossible electrolyte variations and arrhythmias
      ChlorthalidonePossible electrolyte variations and arrhythmias
      CholestyramineThe resin decreases the effect of digoxin
      CinitaprideCinitapride can alter the absorption of digoxin as it simulates gastric emptying.
      ClarithromycinThe macrolide, clarithromycin, may increase the effect of digoxin in 10% of patients.
      ColestipolThe resin decreases the effect of digoxin
      CyclophosphamideThe antineoplasic agent decreases the effect of digoxin
      CyclosporineCyclosporine may increase the effect of digoxin.
      CyclothiazidePossible electrolyte variations and arrhythmias
      CytarabineThe antineoplasic agent decreases the effect of digoxin
      DextrothyroxineThe thyroid hormone, dextrothyroxine, decreases the effect of digoxin.
      DiazepamThe benzodiazepine, diazepam, may increase the effect of digoxin.
      Dihydroquinidine barbiturateQuinine/quinidine increases the effect of digoxin
      DoxorubicinThe antineoplasic agent decreases the effect of digoxin
      DronedaroneDronedarone inhibits P-glycoprotein transporter thus increasing serum concentrations of digoxin 2.5-fold.
      ErythromycinThe macrolide, erythromycin, may increase the effect of digoxin in 10% of patients.
      Ethacrynic acidPossible electrolyte variations and arrhythmias
      EtravirineDigoxin, when administered concomitantly with etravirine, may experience an increase in serum concentration. It is recommended to monitor serum levels of digoxin and titrate dosage to achieve desired therapeutic range. Pre-emptive dose adjustments are not required.
      FurosemidePossible electrolyte variations and arrhythmias
      GatifloxacinGatifloxacin increases the effect of digoxin
      GinsengChanges in digoxin serum levels
      HydrochlorothiazidePossible electrolyte variations and arrhythmias
      HydroflumethiazidePossible electrolyte variations and arrhythmias
      HydroxychloroquineHydroxychloroquine increases the effect of digoxin
      IndapamidePossible electrolyte variations and arrhythmias
      ItraconazoleItraconazole increases the effect of digoxin
      JosamycinThe macrolide, josamycin, may increase the effect of digoxin in 10% of patients.
      LevothyroxineThe thyroid hormone, levothyroxine, decreases the effect of digoxin.
      LiothyronineThe thyroid hormone, liothyronine, decreases the effect of digoxin.
      LiotrixThe thyroid hormone, liotrix, decreases the effect of digoxin.
      LiraglutideThese agents may have decreased C max and a delayed T max during coadministration.
      MethimazoleThe antithyroid agent increases the effect of digoxin
      MethotrexateThe antineoplasic agent decreases the effect of digoxin
      MethyclothiazidePossible electrolyte variations and arrhythmias
      MetolazonePossible electrolyte variations and arrhythmias
      MilnacipranUse of Savella concomitantly with digoxin may be associated with potentiation of adverse hemodynamic effects. Co-administration of Savella and intravenous digoxin should be avoided.
      Mirabegron Mirabegron increased Cmax and AUC of digoxin. Initiate therapy with digoxin at lowest possible dose. Monitor concomitant therapy closely.
      PenbutololBoth digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
      PenciclovirThe multivalent agent decreases the effect of penicillamine
      PenicillaminePenicillamine decreases the effect of digoxin
      PolythiazidePossible electrolyte variations and arrhythmias
      PrazosinPrazosin increases the effect of digoxin
      ProcarbazineThe antineoplasic agent decreases the effect of digoxin
      PropafenonePropafenone increases the effect of digoxin
      PropylthiouracilThe antithyroid agent may increase the effect of digoxin.
      QuinethazonePossible electrolyte variations and arrhythmias
      QuinidineQuinine/quinidine increases the effect of digoxin
      Quinidine barbiturateQuinine/quinidine increases the effect of digoxin
      QuinineQuinine/quinidine increases the effect of digoxin
      RabeprazoleRabeprazole increases the effect of digoxin
      RanolazineRanolazine may increase the serum level of digoxin. Monitor for changes in the serum level and therapeutic and adverse effects of digoxin if ranolazine is initiated, discontinued or dose changed.
      RitonavirRitonavir increases levels/effect of digoxin
      SpironolactoneIncreased digoxin levels and decreased effect in presence of spironolactone
      St. John's WortSt. John's Wort decreases the effect of digoxin
      SulfasalazineSulfasalazine may decrease the effect of digoxin.
      TelaprevirTelaprevir is a substrate of p-glycoprotein and thus increases the AUC and Cmax of digoxin. This indicates an increased absorption of digoxin. Lowest dose of digoxin should be used first and levels be closely monitored.
      TelithromycinTelithromycin may increase the plasma concentration of Digoxin. Monitor for changes in Digoxin efficacy/toxicity if Telithromycin is initiated, discontinued or dose changed.
      TelmisartanTelmisartan may increase plasma Digoxin concentrations. Monitor Digoxin levels and adjust dose as required if Telmisartan is initiated, discontinued or dose changed.
      ThyroglobulinThe thyroid hormone, thyroglobulin, decreases the effect of digoxin.
      TiclopidineTiclopidine may decrease Digoxin levels. Monitor for Digoxin levels with Ticlopidine is initiated, discontinued or dose changed.
      TolbutamideTolbutamide increases the effect of digoxin
      TolvaptanTolvaptan increases serum digoxin concentrations due to competitive inhibition of P-glycoprotein in the liver, intestine, and kidney. P-glycoprotein facilitates digoxin efflux thus inhibition of this protein will increase incidence of adverse effects.
      TrichlormethiazidePossible electrolyte variations and arrhythmias
      TrimetrexateThe absorption of Digoxin, a cardiac glycoside, may be decreased by antineoplastic agents such as Trimetrexate. Liquid forms of Digoxin do not appear to be significantly affected. Monitor Digoxin tablet efficacy if Trimetrexate therapy is initiated, discontinued or if the dose is altered.
      VerapamilVerapamil may increase the serum concentration of Digoxin by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of Digoxin if Verpamail is initiated, discontinued or dose changed.
      VincristineThe antineoplasic agent decreases the effect of digoxin
      VoriconazoleVoriconazole may increase the serum concentration of digoxin. Monitor for increased serum concentrations and toxic effects of digoxin if voriconazole is initiated or dose increased.
      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

      Components

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

      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
      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
      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
      4. Kumar AR, Kurup PA: A hypothalamic digoxin mediated model for conscious and subliminal perception. J Neural Transm. 2001;108(7):855-68. Pubmed
      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

      1. Cholesterol side-chain cleavage enzyme, mitochondrial

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

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

      2. 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

      1. Multidrug resistance protein 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor inducer

      Components

      Name UniProt ID Details
      Multidrug resistance protein 1 P08183 Details

      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
      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
      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
      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
      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
      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
      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
      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
      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
      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
      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
      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
      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
      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
      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
      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
      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. Epub 2009 Jul 21. 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. Solute carrier family 22 member 8

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Solute carrier family 22 member 8 Q8TCC7 Details

      References:

      1. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed

      4. Solute carrier organic anion transporter family member 2B1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 2B1 O94956 Details

      References:

      1. Nishio T, Adachi H, Nakagomi R, Tokui T, Sato E, Tanemoto M, Fujiwara K, Okabe M, Onogawa T, Suzuki T, Nakai D, Shiiba K, Suzuki M, Ohtani H, Kondo Y, Unno M, Ito S, Iinuma K, Nunoki K, Matsuno S, Abe T: Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate. Biochem Biophys Res Commun. 2000 Sep 7;275(3):831-8. Pubmed

      5. Bile salt export pump

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Bile salt export pump O95342 Details

      References:

      1. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. Pubmed

      6. Solute carrier organic anion transporter family member 1A2

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

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

      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
      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

      7. Organic solute transporter subunit alpha

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Organic solute transporter subunit alpha Q86UW1 Details

      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

      8. Organic solute transporter subunit beta

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Organic solute transporter subunit beta Q86UW2 Details

      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

      9. Solute carrier organic anion transporter family member 4A1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 4A1 Q96BD0 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

      10. Solute carrier organic anion transporter family member 1B3

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 1B3 Q9NPD5 Details

      References:

      1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. Pubmed

      11. Solute carrier organic anion transporter family member 1C1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 1C1 Q9NYB5 Details

      References:

      1. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. Pubmed

      12. Solute carrier organic anion transporter family member 1B1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

      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
      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
      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
      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
      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
      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

      Comments
      Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10