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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
12beta-HydroxydigitoxinNot AvailableNot Available
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
DIGOXNot Available
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 KeyLTMHDMANZUZIPE-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
Not Available
3 b-digoxigeninDetails
Digoxin
Not Available
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.
MirabegronMirabegron 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.

Targets

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

Enzymes

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

Transporters

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

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