Spironolactone

Identification

Summary

Spironolactone is an aldosterone receptor antagonist used to treat edema, hypertension, heart failure, and aldosteronism.

Brand Names
Aldactazide, Aldactone, Carospir
Generic Name
Spironolactone
DrugBank Accession Number
DB00421
Background

Spironolactone is a potassium-sparing diuretic. It binds to mineralocorticoid receptors and functions as aldosterone antagonists.6 It promotes sodium and water excretion and potassium retention.7 Spironolactone was originally developed purely for this ability before other pharmacodynamic properties of the drug were discovered.7,10 It is indicated to treat several conditions, including heart failure, edema, hyperaldosteronism, and hypertension.14 Off-label uses of spironolactone include hirsutism, female pattern hair loss, and adult acne vulgaris.4,11

Spironolactone was developed in 1957, marketed in 1959, and approved by the FDA on January 21, 1960.9

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 416.573
Monoisotopic: 416.202130202
Chemical Formula
C24H32O4S
Synonyms
  • Espironolactona
  • Spironolactone
  • Spironolactonum
  • Spironolattone
External IDs
  • NSC-150399
  • SC 9420
  • SC-9420
  • SC9420

Pharmacology

Indication

Spironolactone is indicated for the treatment of the following conditions:

  • NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure. Spironolactone is usually administered in conjunction with other heart failure therapies.14
  • Hypertension, as add-on therapy, in patients not adequately controlled by other agents.14,15
  • Edema associated with hepatic cirrhosis when edema is not responsive to fluid and sodium restriction.14,15
  • Edema associated with nephrotic syndrome when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics produce an inadequate response.14
  • Refractory edema associated with congestive cardiac failure, malignant ascites, hepatic cirrhosis with ascites, and essential hypertension.15
  • Short-term preoperative treatment of patients with primary hyperaldosteronism.14,15
  • Diagnosis of primary aldosteronism.15
  • Long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery.14
  • Long-term maintenance therapy for patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).14

As spironolactone has antiandrogenic activity, its off-label uses include the treatment of hirsutism, female pattern hair loss, and adult acne vulgaris.4,11

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofEdema••••••••••••
Management ofEdema••••••••••••
Management ofHypertension••••••••••••••••• •••••••• •••••••••••• ••••••••••
Diagnostic agentPrimary aldosteronism••••••••••••••••••••••
Management ofPrimary hyperaldosteronism••••••••••••••• • ••••••••• ••• •••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Spironolactone has a potassium-sparing diuretic effect. It promotes sodium and water excretion and potassium retention. It increases renin and aldosterone levels.7 Spironolactone is a mineralocorticoid receptor antagonist and has a low affinity for the glucocorticoid receptor.13 It also exhibits progestogenic and anti-androgenic actions as it binds to the androgen receptor and, to a lesser extent, estrogen and progesterone receptors.7,6,11 Spironolactone exhibits anti-inflammatory effects.6

Mechanism of action

Aldosterone is a key hormone in the renin-angiotensin-aldosterone system. By binding to the mineralocorticoid receptor at the distal tubules and collecting duct, it causes sodium reabsorption and potassium secretion, increases vascular stiffness and remodelling, and activates pro-inflammatory pathways.6,11

Spironolactone and its active metabolites are aldosterone antagonists that produce a potassium-sparing diuretic effect. They competitively bind to 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 that act more proximally in the renal tubule.6,14

TargetActionsOrganism
AMineralocorticoid receptor
antagonist
Humans
UGlucocorticoid receptor
antagonist
Humans
UAndrogen receptor
antagonist
Humans
UProgesterone receptor
agonist
Humans
UEstrogen receptor
agonist
Humans
UNuclear receptor subfamily 1 group I member 2
agonist
Humans
UVoltage-dependent L-type calcium channel
inhibitor
Humans
Absorption

The mean time to reach peak plasma concentration of spironolactone and the active metabolite, canrenone, in healthy volunteers is 2.6 and 4.3 hours, respectively. Food increased the bioavailability of spironolactone (as measured by AUC) by approximately 95.4%.14

Volume of distribution

Not Available

Protein binding

Spironolactone and its metabolites are more than 90% bound to plasma proteins.14 Spironolactone and canrenone bind to serum albumin and alpha 1-acid glycoprotein.1

Metabolism

Spironolactone is rapidly and extensively metabolized to form different metabolites. A group of metabolites are formed when sulfur of spironolactone is removed, such as canrenone. Sulfur is retained in another group of metabolites, including 7-alpha (α)-thiomethylspironolactone (TMS) and 6-beta (ß)-hydroxy-7-alpha (α)-thiomethylspirolactone (HTMS).14

Spironolactone is firstly deacetylated to 7-α-thiospironolactone.2,3,5 7-α-thiospironolactone is S-methylated to TMS, which is the primary metabolite,7,8,12 or dethioacetylated to canrenone.2,3,12 TMS and HTMS can be further metabolized.2,3,12

In humans, the potencies of TMS and 7-α-thiospirolactone in reversing the effects of the synthetic mineralocorticoid, fludrocortisone, on urinary electrolyte composition were approximately a third relative to spironolactone. However, since the serum concentrations of these steroids were not determined, their incomplete absorption and/or first-pass metabolism could not be ruled out as a reason for their reduced in vivo activities.14

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Route of elimination

The metabolites are excreted primarily in the urine and secondarily in bile.14 Metabolites of spironolactone are excreted in urine (42-56%) and in the feces (14.2-14.6%). No unmetabolized spironolactone is present in the urine.5

Half-life

The mean half-life of spironolactone is 1.4 hours. The mean half-life values of its metabolites, including canrenone, TMS, and HTMS are 16.5, 13.8, and 15 hours, respectively.14

Clearance

Not Available

Adverse Effects
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Toxicity

The oral LD50 of spironolactone is greater than 1000 mg/kg in mice, rats, and rabbits.14

Acute overdosage of ALDACTONE may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Rarely, instances of hyponatremia, hyperkalemia,or hepatic coma may occur in patients with severe liver disease, but these are unlikely due to acute overdosage. Hyperkalemia may occur, especially in patients with impaired renal function. In case of an overdose, vomiting may be induced and gastric lavage may be instituted. As there is no specific antidote, treatment is supportive to maintain hydration, electrolyte balance, and vital functions. Patients who have renal impairment may develop hyperkalemia. In such cases, discontinue spironolactone.14

Pathways
PathwayCategory
Spironolactone Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirSpironolactone may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbaloparatideThe risk or severity of adverse effects can be increased when Spironolactone is combined with Abaloparatide.
AbirateroneThe therapeutic efficacy of Abiraterone can be decreased when used in combination with Spironolactone.
AcebutololThe risk or severity of hyperkalemia can be increased when Acebutolol is combined with Spironolactone.
AceclofenacThe risk or severity of hyperkalemia can be increased when Aceclofenac is combined with Spironolactone.
Food Interactions
  • Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
  • Take with or without food. Food increases the bioavailability of spironolactone by approximately 95.4%. It should be taken at a consistent time in regards to food.

Products

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Product Images
International/Other Brands
Osyrol / Spiresis / Spiretic / Spiroctan / Uractone / Verospiron / Xenalon
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AldactoneTablet, film coated100 mg/1OralPfizer Laboratories Div Pfizer Inc1960-01-21Not applicableUS flag
AldactoneTablet, film coated25 mg/1OralREMEDYREPACK INC.2018-08-312020-05-20US flag
AldactoneTablet, film coated50 mg/1OralPfizer Laboratories Div Pfizer Inc1960-01-21Not applicableUS flag
AldactoneTablet, film coated50 mg/1OralPhysicians Total Care, Inc.1995-04-242011-06-30US flag
AldactoneTablet, film coated25 mg/1OralPfizer Laboratories Div Pfizer Inc1960-01-21Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Jamp SpironolactoneTablet100 mgOralJamp Pharma Corporation2022-07-14Not applicableCanada flag
Jamp SpironolactoneTablet25 mgOralJamp Pharma Corporation2022-07-14Not applicableCanada flag
Mint-spironolactoneTablet25 mgOralMint Pharmaceuticals Inc2020-02-06Not applicableCanada flag
Mint-spironolactoneTablet100 mgOralMint Pharmaceuticals Inc2020-02-06Not applicableCanada flag
Ntp-spironolactoneTablet100 mgOralNt Pharma Canada LtdNot applicableNot applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AKTAZİD 25 MG/25 MG FİLM KAPLI TABLET, 100 ADETSpironolactone (25 mg) + Hydrochlorothiazide (25 mg)Tablet, film coatedOralWorld Medicine Ilac San. Ve Tic. a.s.2020-08-14Not applicableTurkey flag
AKTAZİD 25 MG/25 MG FİLM KAPLI TABLET, 20 ADETSpironolactone (25 mg) + Hydrochlorothiazide (25 mg)Tablet, film coatedOralWorld Medicine Ilac San. Ve Tic. a.s.2020-08-14Not applicableTurkey flag
AKTAZİD 25 MG/25 MG FİLM KAPLI TABLET, 30 ADETSpironolactone (25 mg) + Hydrochlorothiazide (25 mg)Tablet, film coatedOralWorld Medicine Ilac San. Ve Tic. a.s.2017-11-02Not applicableTurkey flag
AKTAZİD 25 MG/25 MG FİLM KAPLI TABLET, 50 ADETSpironolactone (25 mg) + Hydrochlorothiazide (25 mg)Tablet, film coatedOralWorld Medicine Ilac San. Ve Tic. a.s.2020-08-14Not applicableTurkey flag
AKTAZİD 50 MG/50 MG FİLM KAPLI TABLET, 100 ADETSpironolactone (50 mg) + Hydrochlorothiazide (50 mg)Tablet, film coatedOralWorld Medicine Ilac San. Ve Tic. a.s.2020-08-14Not applicableTurkey flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
011054 Niacinamide 4% / Spironolactone 5%Spironolactone (5 g/100g) + Nicotinamide (4 g/100g)GelTopicalSincerus Florida, LLC2020-07-02Not applicableUS flag
011218 Niacinamide 2% / Spironolactone 5% / Tretinoin 0.025%Spironolactone (5 g/100g) + Nicotinamide (2 g/100g) + Tretinoin (0.025 g/100g)GelTopicalSincerus Florida, LLC2020-07-02Not applicableUS flag
011220 Niacinamide 2% / Spironolactone 5% / Tretinoin 0.05%Spironolactone (5 g/100g) + Nicotinamide (2 g/100g) + Tretinoin (0.05 g/100g)GelTopicalSincerus Florida, LLC2020-07-02Not applicableUS flag
011503 Dapsone 6% / Niacinamide 2% / Spironolactone 5%Spironolactone (5 g/100g) + Dapsone (6 g/100g) + Nicotinamide (2 g/100g)GelTopicalSincerus Florida, LLC2020-07-02Not applicableUS flag
Benzoyl Peroxide 5% / Clindamycin 1% / Niacinamide 2% / Spironolactone 2%Spironolactone (2 g/100g) + Benzoyl peroxide (5 g/100g) + Clindamycin phosphate (1 g/100g) + Nicotinamide (2 g/100g)GelTopicalSincerus Florida, LLC2019-05-11Not applicableUS flag

Categories

ATC Codes
C03DA01 — Spironolactone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid lactones
Direct Parent
Spironolactones and derivatives
Alternative Parents
3-oxo delta-4-steroids / Delta-4-steroids / Cyclohexenones / Gamma butyrolactones / Tetrahydrofurans / Thioesters / Carboxylic acid esters / Carbothioic S-esters / Sulfenyl compounds / Oxacyclic compounds
show 3 more
Substituents
3-oxo-delta-4-steroid / 3-oxosteroid / Aliphatic heteropolycyclic compound / Carbonyl group / Carbothioic s-ester / Carboxylic acid derivative / Carboxylic acid ester / Cyclic ketone / Cyclohexenone / Delta-4-steroid
show 17 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
thioester, 3-oxo steroid, methyl ketone, oxaspiro compound, steroid lactone (CHEBI:9241) / Pregnane and derivatives [Fig] (C07310)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
27O7W4T232
CAS number
52-01-7
InChI Key
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
(1R,3aS,3bR,4R,9aR,9bS,11aS)-4-(acetylsulfanyl)-9a,11a-dimethyl-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydrospiro[cyclopenta[a]phenanthrene-1,2'-oxolane]-5',7-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

References

Synthesis Reference

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

US4332721
General References
  1. Takamura N, Maruyama T, Ahmed S, Suenaga A, Otagiri M: Interactions of aldosterone antagonist diuretics with human serum proteins. Pharm Res. 1997 Apr;14(4):522-6. [Article]
  2. LaCagnin LB, Lutsie P, Colby HD: Conversion of spironolactone to 7 alpha-thiomethylspironolactone by hepatic and renal microsomes. Biochem Pharmacol. 1987 Oct 15;36(20):3439-44. [Article]
  3. Los LE, Pitzenberger SM, Ramjit HG, Coddington AB, Colby HD: Hepatic metabolism of spironolactone. Production of 3-hydroxy-thiomethyl metabolites. Drug Metab Dispos. 1994 Nov-Dec;22(6):903-8. [Article]
  4. Kim GK, Del Rosso JQ: Oral Spironolactone in Post-teenage Female Patients with Acne Vulgaris: Practical Considerations for the Clinician Based on Current Data and Clinical Experience. J Clin Aesthet Dermatol. 2012 Mar;5(3):37-50. [Article]
  5. Karim A: Spironolactone: disposition, metabolism, pharmacodynamics, and bioavailability. Drug Metab Rev. 1978;8(1):151-88. doi: 10.3109/03602537808993782. [Article]
  6. Carone L, Oxberry SG, Twycross R, Charlesworth S, Mihalyo M, Wilcock A: Spironolactone. J Pain Symptom Manage. 2017 Feb;53(2):288-292. doi: 10.1016/j.jpainsymman.2016.12.320. Epub 2016 Dec 23. [Article]
  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. doi: 10.1007/s10741-005-2345-1. [Article]
  8. Gardiner P, Schrode K, Quinlan D, Martin BK, Boreham DR, Rogers MS, Stubbs K, Smith M, Karim A: Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites. J Clin Pharmacol. 1989 Apr;29(4):342-7. [Article]
  9. Menard J: The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):45-52. doi: 10.1016/j.mce.2003.10.008. [Article]
  10. BOLTE E, VERDY M, MARC-AURELE J, BROUILLET J, BEAUREGARD P, GENEST J: Studies on new diuretic compounds: spirolactone and chlorothiazide. Can Med Assoc J. 1958 Dec 1;79(11):881-8. [Article]
  11. Patibandla S, Heaton J, Kyaw H: Spironolactone. . [Article]
  12. Overdiek HW, Merkus FW: The metabolism and biopharmaceutics of spironolactone in man. Rev Drug Metab Drug Interact. 1987;5(4):273-302. doi: 10.1515/dmdi.1987.5.4.273. [Article]
  13. 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. [Article]
  14. FDA Approved Drug Products: ALDACTONE (spironolactone) tablets, for oral use (December 2022) [Link]
  15. EMA Approved Drug Products: QAIALDO (spironolactone) Oral Suspension [Link]
Human Metabolome Database
HMDB0014565
KEGG Drug
D00443
KEGG Compound
C07310
PubChem Compound
5833
PubChem Substance
46508525
ChemSpider
5628
BindingDB
50228080
RxNav
9997
ChEBI
9241
ChEMBL
CHEMBL1393
ZINC
ZINC000003861599
Therapeutic Targets Database
DAP000297
PharmGKB
PA451483
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
SNL
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Spironolactone
PDB Entries
2ab2 / 2oax / 3vhu
FDA label
Download (204 KB)
MSDS
Download (72.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingBasic ScienceHealthy Volunteers (HV) / Hypoglycemia1
4CompletedDiagnosticHeart Failure1
4CompletedDiagnosticHeart Failure / Nonischemic Dilated Cardiomyopathy1
4CompletedPreventionAnthracycline Induced Cardiotoxicity1
4CompletedPreventionCirrhosis of the Liver / Portal Hypertension1

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
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • A-S Medication Solutions LLC
  • Cardinal Health
  • Caremark LLC
  • Comprehensive Consultant Services Inc.
  • Dept Health Central Pharmacy
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • GD Searle LLC
  • Greenstone LLC
  • Guna Inc.
  • H and H Laboratories
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Neighborcare Repackaging Inc.
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacia Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Professional Co.
  • Qualitest
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Richmond Pharmacy
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • UDL Laboratories
  • Vangard Labs Inc.
  • Vintage Pharmaceuticals Inc.
Dosage Forms
FormRouteStrength
CapsuleOral25 MG
Pill100 MG
Tablet, coatedOral100 MG
CapsuleOral100 mg
Tablet, coatedOral50 mg
TabletOral25.000 mg
TabletOral100. mg
TabletOral2500000 mg
SuspensionOral25 mg/5mL
Tablet, film coatedOral
TabletOral10000000 mg
Capsule, coatedOral
CapsuleOral
GelTopical
CapsuleOral
SuspensionOral10 mg/ml
TabletOral
CapsuleOral50 MG
Tablet, film coatedOral100 mg
Tablet, coatedOral25 mg
Tablet, delayed releaseOral100 mg
TabletOral50 MG
Tablet, film coatedOral50 MG
TabletOral100 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, coatedOral100 mg/1
Tablet, coatedOral25 mg/1
Tablet, coatedOral50 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
TabletOral
Tablet, film coatedOral
TabletOral100 mg
TabletOral25 mg
Tablet, film coatedOral25 mg
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.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9757394No2017-09-122036-10-28US flag
US10493083No2019-12-032036-10-28US flag
US10624906No2020-04-212036-10-28US flag
US10660907No2020-05-262036-10-28US flag
US10888570No2021-01-122036-10-28US flag
US11395828No2016-10-282036-10-28US flag
US11389461No2016-10-282036-10-28US flag
US11491166No2016-10-282036-10-28US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)198-207https://www.fishersci.com/store/msds?partNumber=AC207460050&productDescription=SPIRONOLACTONE+SPIRONOLACT&vendorId=VN00032119&countryCode=US&language=en
logP2.78https://www.ncbi.nlm.nih.gov/pubmed/26642673
Predicted Properties
PropertyValueSource
Water Solubility0.00198 mg/mLALOGPS
logP3.1ALOGPS
logP3.64Chemaxon
logS-5.3ALOGPS
pKa (Strongest Acidic)17.89Chemaxon
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 RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0h2u-0109000000-b5dcae38bb499eaabba7
Mass Spectrum (Electron Ionization)MSsplash10-0006-9836000000-9f600bd39c3b914c0b17
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0000900000-5e2e1944e45fcef225d1
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-014i-0000900000-406c100eed5b6cdc3286
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0005900000-2281d6a738d3d492b753
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-05nf-1229200000-e2d9fa89e5e355517b03
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00xr-2009500000-f64e1194391e1d221187
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-2009300000-5011d7fba923ed4d4aa1
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-06r6-8829100000-6ea2d70d5cb38139b402
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-9007200000-208992f59d97f539818a
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-213.835082
predicted
DarkChem Lite v0.1.0
[M-H]-212.582282
predicted
DarkChem Lite v0.1.0
[M-H]-215.036482
predicted
DarkChem Lite v0.1.0
[M-H]-209.46205
predicted
DeepCCS 1.0 (2019)
[M+H]+214.999482
predicted
DarkChem Lite v0.1.0
[M+H]+213.098082
predicted
DarkChem Lite v0.1.0
[M+H]+215.847282
predicted
DarkChem Lite v0.1.0
[M+H]+211.28694
predicted
DeepCCS 1.0 (2019)
[M+Na]+214.538282
predicted
DarkChem Lite v0.1.0
[M+Na]+212.488382
predicted
DarkChem Lite v0.1.0
[M+Na]+215.573082
predicted
DarkChem Lite v0.1.0
[M+Na]+217.39592
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
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 targ...
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
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. [Article]
  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. [Article]
  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. [Article]
  4. Frishman WH, Stier CT Jr: Aldosterone and aldosterone antagonism in systemic hypertension. Curr Hypertens Rep. 2004 Jun;6(3):195-200. [Article]
  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. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  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. doi: 10.1007/s10741-005-2345-1. [Article]
  8. Rossi G, Boscaro M, Ronconi V, Funder JW: Aldosterone as a cardiovascular risk factor. Trends Endocrinol Metab. 2005 Apr;16(3):104-7. [Article]
  9. FDA Approved Drug Products: ALDACTONE (spironolactone) tablets, for oral use (December 2022) [Link]
Details
2. Glucocorticoid receptor
Kind
Protein
Organism
Humans
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 modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
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. [Article]
  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. [Article]
Details
3. Androgen receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Curator comments
A11837, A178192, A261025
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 ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
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. [Article]
  2. Sica DA: Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. Heart Fail Rev. 2005 Jan;10(1):23-9. doi: 10.1007/s10741-005-2345-1. [Article]
  3. Carone L, Oxberry SG, Twycross R, Charlesworth S, Mihalyo M, Wilcock A: Spironolactone. J Pain Symptom Manage. 2017 Feb;53(2):288-292. doi: 10.1016/j.jpainsymman.2016.12.320. Epub 2016 Dec 23. [Article]
  4. Patibandla S, Heaton J, Kyaw H: Spironolactone. . [Article]
Details
4. Progesterone receptor
Kind
Protein
Organism
Humans
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 ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
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. [Article]
  2. Fernandez MD, Carter GD, Palmer TN: The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol. Br J Clin Pharmacol. 1983 Jan;15(1):95-101. doi: 10.1111/j.1365-2125.1983.tb01470.x. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...

Components:
References
  1. Fernandez MD, Carter GD, Palmer TN: The interaction of canrenone with oestrogen and progesterone receptors in human uterine cytosol. Br J Clin Pharmacol. 1983 Jan;15(1):95-101. doi: 10.1111/j.1365-2125.1983.tb01470.x. [Article]
  2. Levy J, Burshell A, Marbach M, Afllalo L, Glick SM: Interaction of spironolactone with oestradiol receptors in cytosol. J Endocrinol. 1980 Mar;84(3):371-9. doi: 10.1677/joe.0.0840371. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...

Components:
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. [Article]
  2. Dacquet C, Loirand G, Mironneau C, Mironneau J, Pacaud P: Spironolactone inhibition of contraction and calcium channels in rat portal vein. Br J Pharmacol. 1987 Nov;92(3):535-44. doi: 10.1111/j.1476-5381.1987.tb11354.x. [Article]
  3. Mironneau J: Calcium channel antagonist effects of spironolactone, an aldosterone antagonist. Am J Cardiol. 1990 Jun 19;65(23):7K-8K; discussion 3K. doi: 10.1016/0002-9149(90)91267-a. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
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 cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 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. [Article]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
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. [Article]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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
Uniprot Name
Cytochrome P450 11B2, mitochondrial
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. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Takamura N, Maruyama T, Ahmed S, Suenaga A, Otagiri M: Interactions of aldosterone antagonist diuretics with human serum proteins. Pharm Res. 1997 Apr;14(4):522-6. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...

Components:
References
  1. Takamura N, Maruyama T, Ahmed S, Suenaga A, Otagiri M: Interactions of aldosterone antagonist diuretics with human serum proteins. Pharm Res. 1997 Apr;14(4):522-6. [Article]

Transporters

Kind
Protein
Organism
Humans
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
Uniprot Name
Canalicular multispecific organic anion transporter 1
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. [Article]
Details
2. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
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
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Rigalli JP, Ruiz ML, Perdomo VG, Villanueva SS, Mottino AD, Catania VA: Pregnane X receptor mediates the induction of P-glycoprotein by spironolactone in HepG2 cells. Toxicology. 2011 Jul 11;285(1-2):18-24. doi: 10.1016/j.tox.2011.03.015. Epub 2011 Apr 1. [Article]
Kind
Protein
Organism
Humans
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 inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48