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Identification
NameSpironolactone
Accession NumberDB00421  (APRD01234)
TypeSmall Molecule
GroupsApproved
Description

A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)

Structure
Thumb
Synonyms
Espironolactona
Spironolactone
Spironolactonum
Spironolattone
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aldactonetablet, film coated25 mg/1oralG.D. Searle LLC Division of Pfizer Inc1960-01-21Not applicableUs
Aldactonetablet, film coated50 mg/1oralG.D. Searle LLC Division of Pfizer Inc1960-01-21Not applicableUs
Aldactonetablet, film coated100 mg/1oralG.D. Searle LLC Division of Pfizer Inc1960-01-21Not applicableUs
Aldactone 100 mgtablet100 mgoralPfizer Canada Inc1975-12-31Not applicableCanada
Aldactone 25 mgtablet25 mgoralPfizer Canada Inc1959-12-31Not applicableCanada
Ntp-spironolactonetablet100 mgoralNt Pharma Canada LtdNot applicableNot applicableCanada
Ntp-spironolactonetablet25 mgoralNt Pharma Canada LtdNot applicableNot applicableCanada
Spironolactonetablet, film coated100 mg/1oralGreenstone LLC1960-01-21Not applicableUs
Spironolactonetablet, film coated50 mg/1oralGreenstone LLC1960-01-21Not applicableUs
Spironolactonetablet, film coated25 mg/1oralGreenstone LLC1960-01-21Not applicableUs
Spironolactonetablet, film coated50 mg/1oralPd Rx Pharmaceuticals, Inc.1960-01-21Not applicableUs
Teva-spironolactonetablet100 mgoralTeva Canada Limited1984-12-31Not applicableCanada
Teva-spironolactonetablet25 mgoralTeva Canada Limited1984-12-31Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Spironolactonetablet, film coated25 mg/1oralMylan Institutional Inc.1996-12-23Not applicableUs
Spironolactonetablet25 mg/1oralPd Rx Pharmaceuticals, Inc.2010-08-02Not applicableUs
Spironolactonetablet25 mg/1oralBlenheim Pharmacal, Inc.2013-10-02Not applicableUs
Spironolactonetablet25 mg/1oralRebel Distributors Corp1986-07-23Not applicableUs
Spironolactonetablet, film coated100 mg/1oralQualitest Pharmaceuticals2006-08-29Not applicableUs
Spironolactonetablet25 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Spironolactonetablet, film coated50 mg/1oralbryant ranch prepack1986-07-23Not applicableUs
Spironolactonetablet, film coated50 mg/1oralActavis Pharma, Inc.2007-01-03Not applicableUs
Spironolactonetablet25 mg/1oralMutual Pharmaceutical Company, Inc.1986-07-23Not applicableUs
Spironolactonetablet, film coated25 mg/1oralCardinal Health2011-05-192016-03-02Us
Spironolactonetablet, film coated25 mg/1oralA S Medication Solutions2006-08-29Not applicableUs
Spironolactonetablet, film coated50 mg/1oralMylan Institutional Inc.2002-02-20Not applicableUs
Spironolactonetablet25 mg/1oralState of Florida DOH Central Pharmacy2013-01-01Not applicableUs
Spironolactonetablet, film coated50 mg/1oralAmerican Health Packaging2011-06-10Not applicableUs
Spironolactonetablet50 mg/1oralMc Kesson Packaging Services Business Unit Of Mc Kesson Corporation2009-08-18Not applicableUs
Spironolactonetablet, film coated25 mg/1oralSandoz Inc1982-01-01Not applicableUs
Spironolactonetablet25 mg/1oralUnit Dose Services1986-07-23Not applicableUs
Spironolactonetablet, film coated25 mg/1oralRebel Distributors Corp2007-01-03Not applicableUs
Spironolactonetablet25 mg/1oralBlenheim Pharmacal, Inc.2014-02-12Not applicableUs
Spironolactonetablet, film coated50 mg/1oralQualitest Pharmaceuticals2006-08-29Not applicableUs
Spironolactonetablet, film coated25 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Spironolactonetablet, film coated100 mg/1oralbryant ranch prepack1986-07-23Not applicableUs
Spironolactonetablet25 mg/1oralREMEDYREPACK INC.2014-06-24Not applicableUs
Spironolactonetablet, film coated25 mg/1oralCardinal Health2011-02-04Not applicableUs
Spironolactonetablet25 mg/1oralAvera Mc Kennan Hospital2015-03-24Not applicableUs
Spironolactonetablet, film coated25 mg/1oralAmerican Health Packaging2010-04-14Not applicableUs
Spironolactonetablet, film coated100 mg/1oralUnit Dose Services1986-07-23Not applicableUs
Spironolactonetablet, film coated50 mg/1oralLake Erie Medical DBA Quality Care Products LLC2007-01-03Not applicableUs
Spironolactonetablet100 mg/1oralMajor Pharmaceuticals2009-11-02Not applicableUs
Spironolactonetablet, film coated25 mg/1oralQualitest Pharmaceuticals2006-08-29Not applicableUs
Spironolactonetablet, film coated100 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Spironolactonetablet25 mg/1oralbryant ranch prepack1986-07-23Not applicableUs
Spironolactonetablet25 mg/1oralREMEDYREPACK INC.2014-04-16Not applicableUs
Spironolactonetablet, film coated50 mg/1oralCardinal Health2011-02-04Not applicableUs
Spironolactonetablet, film coated25 mg/1oralMc Kesson Contract Packaging2011-12-07Not applicableUs
Spironolactonetablet, film coated25 mg/1oralDispensing Solutions, Inc.2006-08-29Not applicableUs
Spironolactonetablet, film coated50 mg/1oralUnit Dose Services1986-07-23Not applicableUs
Spironolactonetablet, film coated100 mg/1oralLake Erie Medical DBA Quality Care Products LLC2011-04-15Not applicableUs
Spironolactonetablet50 mg/1oralMajor Pharmaceuticals2009-11-02Not applicableUs
Spironolactonetablet, film coated25 mg/1oralMylan Pharmaceuticals Inc.1981-02-03Not applicableUs
Spironolactonetablet100 mg/1oralAmneal Pharmaceuticals of New York, LLC2010-08-02Not applicableUs
Spironolactonetablet25 mg/1oralSt Marys Medical Park Pharmacy2013-05-22Not applicableUs
Spironolactonetablet25 mg/1oralREMEDYREPACK INC.2013-05-28Not applicableUs
Spironolactonetablet, film coated100 mg/1oralCardinal Health2011-02-04Not applicableUs
Spironolactonetablet25 mg/1oralPreferred Pharmaceuticals, Inc.2012-10-31Not applicableUs
Spironolactonetablet100 mg/1oralAmneal Pharmaceuticals of New York, LLC2010-08-02Not applicableUs
Spironolactonetablet25 mg/1oralMajor Pharmaceuticals2009-11-02Not applicableUs
Spironolactonetablet, film coated100 mg/1oralMylan Pharmaceuticals Inc.2002-01-22Not applicableUs
Spironolactonetablet50 mg/1oralAmneal Pharmaceuticals of New York, LLC2010-08-02Not applicableUs
Spironolactonetablet, film coated100 mg/1oralJubilant Cadista Pharmaceuticals Inc.2013-02-01Not applicableUs
Spironolactonetablet25 mg/1oralREMEDYREPACK INC.2013-05-28Not applicableUs
Spironolactonetablet25 mg/1oralCardinal Health2011-06-01Not applicableUs
Spironolactonetablet, film coated50 mg/1oralPreferred Pharmaceuticals, Inc.2014-10-17Not applicableUs
Spironolactonetablet50 mg/1oralAmneal Pharmaceuticals of New York, LLC2010-08-02Not applicableUs
Spironolactonetablet25 mg/1oralAv Pak2011-05-19Not applicableUs
Spironolactonetablet, film coated50 mg/1oralAidarex Pharmaceuticals LLC2006-08-29Not applicableUs
Spironolactonetablet25 mg/1oralPreferred Pharmaceuticals, Inc1994-03-25Not applicableUs
Spironolactonetablet25 mg/1oralAmneal Pharmaceuticals of New York, LLC2010-08-02Not applicableUs
Spironolactonetablet25 mg/1oralA S Medication Solutions Llc1986-07-23Not applicableUs
Spironolactonetablet, film coated25 mg/1oralAidarex Pharmaceuticals LLC2006-08-29Not applicableUs
Spironolactonetablet, film coated100 mg/1oralNcs Health Care Of Ky, Inc Dba Vangard Labs2001-08-20Not applicableUs
Spironolactonetablet, film coated50 mg/1oralMylan Pharmaceuticals Inc.2002-01-22Not applicableUs
Spironolactonetablet25 mg/1oralAmneal Pharmaceuticals of New York, LLC2010-08-02Not applicableUs
Spironolactonetablet, film coated50 mg/1oralJubilant Cadista Pharmaceuticals Inc.2013-02-01Not applicableUs
Spironolactonetablet, film coated25 mg/1oralREMEDYREPACK INC.2013-06-04Not applicableUs
Spironolactonetablet, film coated100 mg/1oralPhysicians Total Care, Inc.2004-03-09Not applicableUs
Spironolactonetablet25 mg/1oralREMEDYREPACK INC.2011-05-12Not applicableUs
Spironolactonetablet, film coated100 mg/1oralAidarex Pharmaceuticals LLC2006-08-29Not applicableUs
Spironolactonetablet, film coated50 mg/1oralNcs Health Care Of Ky, Inc Dba Vangard Labs2001-08-20Not applicableUs
Spironolactonetablet, film coated25 mg/1oralActavis Pharma, Inc.2007-01-03Not applicableUs
Spironolactonetablet, film coated100 mg/1oralMutual Pharmaceutical Company, Inc.1986-07-23Not applicableUs
Spironolactonetablet, film coated25 mg/1oralJubilant Cadista Pharmaceuticals Inc.2013-02-01Not applicableUs
Spironolactonetablet, film coated25 mg/1oralNorthwind Pharmaceuticals, LLC2014-09-15Not applicableUs
Spironolactonetablet, film coated50 mg/1oralPhysicians Total Care, Inc.2003-09-11Not applicableUs
Spironolactonetablet, film coated25 mg/1oralCarilion Materials Management2007-01-03Not applicableUs
Spironolactonetablet50 mg/1oralMc Kesson Packaging Services A Business Unit Of Mc Kesson Corporation2011-06-01Not applicableUs
Spironolactonetablet25 mg/1oralREMEDYREPACK INC.2011-10-07Not applicableUs
Spironolactonetablet, film coated50 mg/1oralRebel Distributors Corp2006-08-29Not applicableUs
Spironolactonetablet, film coated25 mg/1oralNcs Health Care Of Ky, Inc Dba Vangard Labs2001-08-20Not applicableUs
Spironolactonetablet, film coated100 mg/1oralActavis Pharma, Inc.2007-01-03Not applicableUs
Spironolactonetablet, film coated50 mg/1oralMutual Pharmaceutical Company, Inc.1986-07-23Not applicableUs
Spironolactonetablet, film coated25 mg/1oralPd Rx Pharmaceuticals, Inc.2006-08-29Not applicableUs
Spironolactonetablet, film coated100 mg/1oralMylan Institutional Inc.2002-02-20Not applicableUs
Spironolactonetablet, film coated25 mg/1oralPhysicians Total Care, Inc.1994-03-25Not applicableUs
Spironolactonetablet, film coated100 mg/1oralAmerican Health Packaging2011-06-10Not applicableUs
Spironolactonetablet25 mg/1oralMc Kesson Packaging Services A Business Unit Of Mc Kesson Corporation2011-06-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
OsyrolNot Available
SpiresisNot Available
SpireticNot Available
SpiroctanNot Available
UractoneNot Available
VerospironNot Available
XenalonNot Available
Brand mixtures
NameLabellerIngredients
AldactazideG.D. Searle LLC Division of Pfizer Inc
Aldactazide 25Pfizer Canada Inc
Aldactazide 50Pfizer Canada Inc
Apo-spirozide TabApotex Inc
Spironolactone and HydrochlorothiazideMylan Pharmaceuticals Inc.
Teva-spironolactone/hctzTeva Canada Limited
SaltsNot Available
Categories
UNII27O7W4T232
CAS number52-01-7
WeightAverage: 416.573
Monoisotopic: 416.202130202
Chemical FormulaC24H32O4S
InChI KeyInChIKey=LXMSZDCAJNLERA-ZHYRCANASA-N
InChI
InChI=1S/C24H32O4S/c1-14(25)29-19-13-15-12-16(26)4-8-22(15,2)17-5-9-23(3)18(21(17)19)6-10-24(23)11-7-20(27)28-24/h12,17-19,21H,4-11,13H2,1-3H3/t17-,18-,19+,21+,22-,23-,24+/m0/s1
IUPAC Name
(1'S,2R,2'R,9'R,10'R,11'S,15'S)-9'-(acetylsulfanyl)-2',15'-dimethylspiro[oxolane-2,14'-tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan]-6'-ene-5,5'-dione
SMILES
[H][C@@]12CC[C@@]3(CCC(=O)O3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])[C@@]([H])(CC2=CC(=O)CC[C@]12C)SC(C)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as spironolactones and derivatives. These are steroid lactones with a structure based on the spironolactone skeleton.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassSteroid lactones
Direct ParentSpironolactones and derivatives
Alternative Parents
Substituents
  • Spironolactone
  • Oxosteroid
  • 3-oxosteroid
  • 3-oxo-delta-4-steroid
  • Delta-4-steroid
  • Gamma butyrolactone
  • Oxolane
  • Cyclic ketone
  • Thiocarboxylic acid ester
  • Lactone
  • Ketone
  • Carboxylic acid ester
  • Oxacycle
  • Organoheterocyclic compound
  • Sulfenyl compound
  • Thioether
  • Thiocarboxylic acid or derivatives
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed primarily to treat low-renin hypertension, hypokalemia, and Conn's syndrome.
PharmacodynamicsSpironolactone is a synthetic 17-lactone steroid which is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics. On its own, spironolactone is only a weak diuretic, but it can be combined with other diuretics. Due to its anti-androgen effect, it can also be used to treat hirsutism, and is a common component in hormone therapy for male-to-female transgendered people. Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptor in the distal tubule cells. This increases the secretion of water and sodium, while decreasing the excretion of potassium. Spironolactone has a fairly slow onset of action, taking several days to develop and similarly the effect diminishes slowly.
Mechanism of actionSpironolactone is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents which act more proximally in the renal tubule. Aldosterone interacts with a cytoplasmic mineralocorticoid receptor to enhance the expression of the Na+, K+-ATPase and the Na+ channel involved in a Na+ K+ transport in the distal tubule . Spironolactone bind to this mineralcorticoid receptor, blocking the actions of aldosterone on gene expression. Aldosterone is a hormone; its primary function is to retain sodium and excrete potassium in the kidneys.
Related Articles
AbsorptionFairly rapidly absorbed from the gastrointestinal tract. Food increases the bioavailability of unmetabolized spironolactone by almost 100%.
Volume of distributionNot Available
Protein bindingSpironolactone and its metabolites are more than 90% bound to plasma proteins.
Metabolism

Rapidly and extensively metabolized. The metabolic pathway of spironolactone is complex and can be divided into two main routes: those in which the sulfur moiety is retained and those in which the sulfur moiety is removed by dethioacetylation. Spironolactone is transformed to a reactive metabolite that can inactivate adrenal and testicular cytochrome P450 enzymes. It also has anti-androgenic activity.

Route of eliminationThe metabolites are excreted primarily in the urine and secondarily in bile.
Half life10 minutes
ClearanceNot Available
ToxicityThe oral LD50 of spironolactone is greater than 1,000 mg/kg in mice, rats, and rabbits. Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Spironolactone Action PathwayDrug actionSMP00134
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9912
Blood Brain Barrier+0.932
Caco-2 permeable+0.5432
P-glycoprotein substrateSubstrate0.5691
P-glycoprotein inhibitor IInhibitor0.6807
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterNon-inhibitor0.727
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6638
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9276
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8681
Ames testNon AMES toxic0.9158
CarcinogenicityNon-carcinogens0.9288
BiodegradationNot ready biodegradable0.9696
Rat acute toxicity2.0150 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9427
hERG inhibition (predictor II)Non-inhibitor0.7002
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Gd searle llc
  • Actavis elizabeth llc
  • Amneal pharmaceuticals
  • Ascot hosp pharmaceuticals inc div travenol laboratories inc
  • Ivax pharmaceuticals inc
  • Lederle laboratories div american cyanamid co
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Superpharm corp
  • Upsher smith laboratories inc
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals llc
  • Warner chilcott div warner lambert co
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedoral
Tablet, film coatedoral100 mg/1
Tablet, film coatedoral25 mg/1
Tablet, film coatedoral50 mg/1
Tabletoral100 mg
Tabletoral25 mg
Tabletoral100 mg/1
Tabletoral25 mg/1
Tabletoral50 mg/1
Tabletoral
Prices
Unit descriptionCostUnit
Spironolactone powder12.56USD g
Aldactone 100 mg tablet2.14USD tablet
Aldactazide 50-50 mg tablet2.02USD tablet
Aldactazide 50-50 tablet1.92USD tablet
Aldactone 50 mg tablet1.84USD tablet
Spironolactone 100 mg tablet1.45USD tablet
Aldactazide 25-25 mg tablet1.26USD tablet
Aldactazide 25-25 tablet1.04USD tablet
Spironolactone 50 mg tablet0.83USD tablet
Aldactone 25 mg tablet0.8USD tablet
Spironolactone-HCTZ 25-25 mg tablet0.57USD tablet
Spironolactone 25 mg tablet0.5USD tablet
Novo-Spiroton 100 mg Tablet0.25USD tablet
Novo-Spiroton 25 mg Tablet0.11USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point134.5 °CPhysProp
water solubility22 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.78HANSCH,C ET AL. (1995)
logS-4.28ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.00198 mg/mLALOGPS
logP3.1ALOGPS
logP3.64ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)18.01ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area60.44 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity113.5 m3·mol-1ChemAxon
Polarizability46.03 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-0006-9836000000-9f600bd39c3b914c0b17View in MoNA
References
Synthesis Reference

Giuseppe Bernini, “Process for preparing micronized spironolactone.” U.S. Patent US4332721, issued July, 1975.

US4332721
General References
  1. Berardesca E, Gabba P, Ucci G, Borroni G, Rabbiosi G: Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris. Int J Tissue React. 1988;10(2):115-9. [PubMed:2972662 ]
  2. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17. [PubMed:10471456 ]
  3. Wandelt-Freerksen E: [Aldactone in the treatment of sarcoidosis of the lungs (author's transl)]. Z Erkr Atmungsorgane. 1977 Jul;149(1):156-9. [PubMed:607621 ]
External Links
ATC CodesC03DA01
AHFS Codes
  • 24:32.20
PDB EntriesNot Available
FDA labelDownload (395 KB)
MSDSDownload (72.6 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe therapeutic efficacy of Abiraterone can be decreased when used in combination with Spironolactone.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Spironolactone.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Spironolactone.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Spironolactone.
AlfuzosinAlfuzosin may increase the hypotensive activities of Spironolactone.
AmifostineSpironolactone may increase the hypotensive activities of Amifostine.
AmilorideAmiloride may increase the hyperkalemic activities of Spironolactone.
Ammonium chlorideThe risk or severity of adverse effects can be increased when Spironolactone is combined with Ammonium chloride.
ArdeparinArdeparin may increase the hyperkalemic activities of Spironolactone.
AtorvastatinThe risk or severity of adverse effects can be increased when Atorvastatin is combined with Spironolactone.
Atracurium besylateSpironolactone may increase the neuromuscular blocking activities of Atracurium besylate.
BrimonidineBrimonidine may increase the antihypertensive activities of Spironolactone.
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Spironolactone.
ButabarbitalButabarbital may increase the hypotensive activities of Spironolactone.
ButethalButethal may increase the hypotensive activities of Spironolactone.
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Spironolactone.
CaffeineThe risk or severity of adverse effects can be increased when Caffeine is combined with Spironolactone.
CanagliflozinCanagliflozin may increase the hyperkalemic activities of Spironolactone.
ChlorphenamineThe risk or severity of adverse effects can be increased when Chlorphenamine is combined with Spironolactone.
CholestyramineThe risk or severity of adverse effects can be increased when Cholestyramine is combined with Spironolactone.
CiprofloxacinSpironolactone may increase the arrhythmogenic activities of Ciprofloxacin.
Cisatracurium besylateSpironolactone may increase the neuromuscular blocking activities of Cisatracurium besylate.
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Spironolactone.
CyclosporineSpironolactone may increase the hyperkalemic activities of Cyclosporine.
DiazoxideDiazoxide may increase the hypotensive activities of Spironolactone.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Spironolactone.
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Spironolactone.
DipivefrinSpironolactone may decrease the vasoconstricting activities of Dipivefrin.
DopamineSpironolactone may decrease the vasoconstricting activities of Dopamine.
DrospirenoneDrospirenone may increase the hyperkalemic activities of Spironolactone.
DuloxetineSpironolactone may increase the orthostatic hypotensive activities of Duloxetine.
EphedrineSpironolactone may decrease the vasoconstricting activities of Ephedrine.
EpinephrineSpironolactone may decrease the vasoconstricting activities of Epinephrine.
EplerenoneEplerenone may increase the hyperkalemic activities of Spironolactone.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Spironolactone.
HeparinHeparin may increase the hyperkalemic activities of Spironolactone.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Spironolactone.
HexobarbitalHexobarbital may increase the hypotensive activities of Spironolactone.
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Spironolactone.
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Spironolactone.
InfliximabInfliximab may decrease the antihypertensive activities of Spironolactone.
LevodopaSpironolactone may increase the orthostatic hypotensive activities of Levodopa.
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Spironolactone.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Spironolactone.
MethohexitalMethohexital may increase the hypotensive activities of Spironolactone.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Spironolactone.
MitotaneThe therapeutic efficacy of Mitotane can be decreased when used in combination with Spironolactone.
MolsidomineMolsidomine may increase the hypotensive activities of Spironolactone.
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Spironolactone.
MoxonidineMoxonidine may increase the hypotensive activities of Spironolactone.
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Spironolactone.
NicorandilNicorandil may increase the hypotensive activities of Spironolactone.
NitrofurantoinNitrofurantoin may increase the hyperkalemic activities of Spironolactone.
NorepinephrineSpironolactone may decrease the vasoconstricting activities of Norepinephrine.
ObinutuzumabSpironolactone may increase the hypotensive activities of Obinutuzumab.
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Spironolactone.
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Spironolactone.
PancuroniumSpironolactone may increase the neuromuscular blocking activities of Pancuronium.
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Spironolactone.
PentobarbitalPentobarbital may increase the hypotensive activities of Spironolactone.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Spironolactone.
PerindoprilSpironolactone may increase the hyperkalemic activities of Perindopril.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Spironolactone.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Spironolactone.
PrimidonePrimidone may increase the hypotensive activities of Spironolactone.
PseudoephedrineSpironolactone may decrease the vasoconstricting activities of Pseudoephedrine.
QuinidineThe therapeutic efficacy of Quinidine can be decreased when used in combination with Spironolactone.
QuinineQuinine may increase the hypotensive activities of Spironolactone.
RacepinephrineSpironolactone may decrease the vasoconstricting activities of Racepinephrine.
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Spironolactone.
RisperidoneSpironolactone may increase the hypotensive activities of Risperidone.
RituximabSpironolactone may increase the hypotensive activities of Rituximab.
RocuroniumSpironolactone may increase the neuromuscular blocking activities of Rocuronium.
SecobarbitalSecobarbital may increase the hypotensive activities of Spironolactone.
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Spironolactone.
TacrolimusSpironolactone may increase the hyperkalemic activities of Tacrolimus.
TadalafilTadalafil may increase the antihypertensive activities of Spironolactone.
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Spironolactone.
TolvaptanTolvaptan may increase the hyperkalemic activities of Spironolactone.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Spironolactone.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Spironolactone.
TreprostinilTreprostinil may increase the hypotensive activities of Spironolactone.
TriamtereneTriamterene may increase the hyperkalemic activities of Spironolactone.
TrimethoprimTrimethoprim may increase the hyperkalemic activities of Spironolactone.
TriprolidineSpironolactone may decrease the vasoconstricting activities of Triprolidine.
ValsartanValsartan may increase the hyperkalemic activities of Spironolactone.
VardenafilVardenafil may increase the antihypertensive activities of Spironolactone.
VecuroniumSpironolactone may increase the neuromuscular blocking activities of Vecuronium.
YohimbineYohimbine may decrease the antihypertensive activities of Spironolactone.
Food Interactions
  • Avoid alcohol.
  • Food increases the bioavailability of spironolactone by almost 100%.
  • Spironolactone may decrease the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Zinc ion binding
Specific Function:
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.
Gene Name:
NR3C2
Uniprot ID:
P08235
Molecular Weight:
107066.575 Da
References
  1. Sitruk-Ware R: Progestogens in hormonal replacement therapy: new molecules, risks, and benefits. Menopause. 2002 Jan-Feb;9(1):6-15. [PubMed:11791081 ]
  2. Rogerson FM, Yao YZ, Smith BJ, Dimopoulos N, Fuller PJ: Determinants of spironolactone binding specificity in the mineralocorticoid receptor. J Mol Endocrinol. 2003 Dec;31(3):573-82. [PubMed:14664717 ]
  3. Gertner RA, Klein JD, Bailey JL, Kim DU, Luo XH, Bagnasco SM, Sands JM: Aldosterone decreases UT-A1 urea transporter expression via the mineralocorticoid receptor. J Am Soc Nephrol. 2004 Mar;15(3):558-65. [PubMed:14978157 ]
  4. Frishman WH, Stier CT Jr: Aldosterone and aldosterone antagonism in systemic hypertension. Curr Hypertens Rep. 2004 Jun;6(3):195-200. [PubMed:15128471 ]
  5. Rogerson FM, Yao Y, Smith BJ, Fuller PJ: Differences in the determinants of eplerenone, spironolactone and aldosterone binding to the mineralocorticoid receptor. Clin Exp Pharmacol Physiol. 2004 Oct;31(10):704-9. [PubMed:15554912 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Sica DA: Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. Heart Fail Rev. 2005 Jan;10(1):23-9. [PubMed:15947888 ]
  8. Rossi G, Boscaro M, Ronconi V, Funder JW: Aldosterone as a cardiovascular risk factor. Trends Endocrinol Metab. 2005 Apr;16(3):104-7. [PubMed:15808807 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Zinc ion binding
Specific Function:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
References
  1. Ye P, Yamashita T, Pollock DM, Sasano H, Rainey WE: Contrasting effects of eplerenone and spironolactone on adrenal cell steroidogenesis. Horm Metab Res. 2009 Jan;41(1):35-9. doi: 10.1055/s-0028-1087188. Epub 2008 Sep 25. [PubMed:18819053 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial ...
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
References
  1. Fagart J, Hillisch A, Huyet J, Barfacker L, Fay M, Pleiss U, Pook E, Schafer S, Rafestin-Oblin ME, Kolkhof P: A new mode of mineralocorticoid receptor antagonism by a potent and selective nonsteroidal molecule. J Biol Chem. 2010 Sep 24;285(39):29932-40. doi: 10.1074/jbc.M110.131342. Epub 2010 Jul 22. [PubMed:20650892 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Zinc ion binding
Specific Function:
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon grow...
Gene Name:
NR3C1
Uniprot ID:
P04150
Molecular Weight:
85658.57 Da
References
  1. Fagart J, Hillisch A, Huyet J, Barfacker L, Fay M, Pleiss U, Pook E, Schafer S, Rafestin-Oblin ME, Kolkhof P: A new mode of mineralocorticoid receptor antagonism by a potent and selective nonsteroidal molecule. J Biol Chem. 2010 Sep 24;285(39):29932-40. doi: 10.1074/jbc.M110.131342. Epub 2010 Jul 22. [PubMed:20650892 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Steroid 11-beta-monooxygenase activity
Specific Function:
Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
Gene Name:
CYP11B2
Uniprot ID:
P19099
Molecular Weight:
57559.62 Da
References
  1. Cheng SC, Suzuki K, Sadee W, Harding BW: Effects of spironolactone, canrenone and canrenoate-K on cytochrome P450, and 11beta- and 18-hydroxylation in bovine and human adrenal cortical mitochondria. Endocrinology. 1976 Oct;99(4):1097-106. [PubMed:976190 ]
6. 17alpha-hydroxylase
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
References
  1. Authors unspecified: Spironolactone and endocrine dysfunction. Ann Intern Med. 1976 Nov;85(5):630-6. [PubMed:984618 ]
  2. Desai; Meena P.; Vijayalakshmi Bhatia & P.S.N. Menon (2001). Pediatric Endocrine Disorders. Orient Blackswan. [ISBN:978-81-250-2025-7 ]
7. 17,20-desmolase
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
References
  1. Authors unspecified: Spironolactone and endocrine dysfunction. Ann Intern Med. 1976 Nov;85(5):630-6. [PubMed:984618 ]
  2. Desai; Meena P.; Vijayalakshmi Bhatia & P.S.N. Menon (2001). Pediatric Endocrine Disorders. Orient Blackswan. [ISBN:978-81-250-2025-7 ]
Kind
Protein group
Organism
Pharmacological action
unknown
Actions
antagonist
General Function:
Electron carrier activity
Specific Function:
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
Components:
NameUniProt IDDetails
3-oxo-5-alpha-steroid 4-dehydrogenase 1P18405 Details
3-oxo-5-alpha-steroid 4-dehydrogenase 2P31213 Details
Polyprenol reductaseQ9H8P0 Details
References
  1. Corvol P, Michaud A, Menard J, Freifeld M, Mahoudeau J: Antiandrogenic effect of spirolactones: mechanism of action. Endocrinology. 1975 Jul;97(1):52-8. [PubMed:166833 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Androgen binding
Specific Function:
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration.
Gene Name:
SHBG
Uniprot ID:
P04278
Molecular Weight:
43778.755 Da
References
  1. Braunstein GD: Clinical practice. Gynecomastia. N Engl J Med. 2007 Sep 20;357(12):1229-37. [PubMed:17881754 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated calcium channel activity
Specific Function:
This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex.
Gene Name:
CACNG1
Uniprot ID:
Q06432
Molecular Weight:
25028.105 Da
References
  1. Sorrentino R, Autore G, Cirino G, d'Emmanuele de Villa Bianca R, Calignano A, Vanasia M, Alfieri C, Sorrentino L, Pinto A: Effect of spironolactone and its metabolites on contractile property of isolated rat aorta rings. J Cardiovasc Pharmacol. 2000 Aug;36(2):230-5. [PubMed:10942165 ]
  2. Melander A, Danielson K, Schersten B, Thulin T, Wahlin E: Enhancement by food of canrenone bioavailability from spironolactone. Clin Pharmacol Ther. 1977 Jul;22(1):100-3. [PubMed:872489 ]
11. Dihydrotestosterone receptor
Kind
Protein
Organism
Human
Pharmacological action
unknown
References
  1. Berardesca E, Gabba P, Ucci G, Borroni G, Rabbiosi G: Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris. Int J Tissue React. 1988;10(2):115-9. [PubMed:2972662 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807 ]
  2. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitorinducer
General Function:
Steroid 11-beta-monooxygenase activity
Specific Function:
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB.
Gene Name:
CYP11B1
Uniprot ID:
P15538
Molecular Weight:
57572.44 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Cheng SC, Suzuki K, Sadee W, Harding BW: Effects of spironolactone, canrenone and canrenoate-K on cytochrome P450, and 11beta- and 18-hydroxylation in bovine and human adrenal cortical mitochondria. Endocrinology. 1976 Oct;99(4):1097-106. [PubMed:976190 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
References
  1. Johnson DR, Klaassen CD: Regulation of rat multidrug resistance protein 2 by classes of prototypical microsomal enzyme inducers that activate distinct transcription pathways. Toxicol Sci. 2002 Jun;67(2):182-9. [PubMed:12011477 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Wang E, Lew K, Barecki M, Casciano CN, Clement RP, Johnson WW: Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4. Chem Res Toxicol. 2001 Dec;14(12):1596-603. [PubMed:11743742 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibited by the grapefruit juice component naringin.
Gene Name:
SLCO1A2
Uniprot ID:
P46721
Molecular Weight:
74144.105 Da
References
  1. Kanai N, Lu R, Bao Y, Wolkoff AW, Schuster VL: Transient expression of oatp organic anion transporter in mammalian cells: identification of candidate substrates. Am J Physiol. 1996 Feb;270(2 Pt 2):F319-25. [PubMed:8779893 ]
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Drug created on June 13, 2005 07:24 / Updated on April 21, 2016 14:06