U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C15H10O2
Molecular Weight 222.2387
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHENINDIONE

SMILES

O=C1C(C(=O)C2=C1C=CC=C2)C3=CC=CC=C3

InChI

InChIKey=NFBAXHOPROOJAW-UHFFFAOYSA-N
InChI=1S/C15H10O2/c16-14-11-8-4-5-9-12(11)15(17)13(14)10-6-2-1-3-7-10/h1-9,13H

HIDE SMILES / InChI
Phenindione is an anticoagulant which functions as a Vitamin K antagonist. The drug was discontinued in USA, but still in use worldwide.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
HEDULIN

Approved Use

Phenindione is a synthetic anticoagulant which acts by interfering with the formation of factors II, VII, IX and X. It produces its effect in 36-48 hours after the initial dose; the effect wanes over a period of 48-72 hours after phenindione is stopped.
Primary
HEDULIN

Approved Use

Phenindione is a synthetic anticoagulant which acts by interfering with the formation of factors II, VII, IX and X. It produces its effect in 36-48 hours after the initial dose; the effect wanes over a period of 48-72 hours after phenindione is stopped.
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
175 μg/mL
30 mg/kg single, intravenous
dose: 30 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PHENINDIONE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
393 μg × h/mL
30 mg/kg single, intravenous
dose: 30 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PHENINDIONE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2 h
30 mg/kg single, intravenous
dose: 30 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PHENINDIONE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5 h
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENINDIONE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
12%
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENINDIONE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
75 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, 53 years
n = 1
Health Status: unhealthy
Age Group: 53 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Jaundice...
AEs leading to
discontinuation/dose reduction:
Jaundice (1 patient)
Sources:
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 63 years
n = 1
Health Status: unhealthy
Age Group: 63 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Jaundice...
AEs leading to
discontinuation/dose reduction:
Jaundice (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Jaundice 1 patient
Disc. AE
75 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 75 mg, 1 times / day
Route: oral
Route: multiple
Dose: 75 mg, 1 times / day
Sources:
unhealthy, 53 years
n = 1
Health Status: unhealthy
Age Group: 53 years
Sex: M
Population Size: 1
Sources:
Jaundice 1 patient
Disc. AE
100 mg 1 times / day multiple, oral (mean)
Studied dose
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, 63 years
n = 1
Health Status: unhealthy
Age Group: 63 years
Sex: M
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
slight or no effect
slight or no effect
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
likely
PubMed

PubMed

TitleDatePubMed
Sustained release of propranolol hydrochloride based on ion-exchange resin entrapped within polystyrene microcapsules.
2006 Dec
Acute immuno-allergic interstitial nephritis caused by fluindione.
2006 Dec
Vitamin K antagonists and pregnancy outcome. A multi-centre prospective study.
2006 Jun
Preparation and in vitro evaluation of polystyrene-coated diltiazem-resin complex by oil-in-water emulsion solvent evaporation method.
2006 May 26
A green method for the electroorganic synthesis of new 1,3-Indandione derivatives.
2006 Oct
Can cryoglobulins interfere with the measurement of IgM antiphosphatidylethanolamine antibodies by ELISA?
2007
Descriptive analysis of the process and quality of oral anticoagulation management in real-life practice in patients with chronic non-valvular atrial fibrillation: the international study of anticoagulation management (ISAM).
2007 Apr
[Advice for patients taking oral anticoagulants (coumadin or Previscan)].
2007 Apr 15
Identification of selective ion-exchange resin for fluoride sorption.
2007 Apr 15
Acute thrombosis of a prosthetic mitral valve: a lesson in anticoagulation.
2007 Aug
[Liver toxicity associated with oral anticoagulant treatment: report of two cases].
2007 Jun-Jul
Iron and manganese contamination: sources, adverse effects and control methods.
2007 Oct
Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis.
2007 Oct
[Modification of an antitumor action of photodynamic therapy with anticoagulant drug fenylin].
2007 Oct-Dec
Taste mask, design and evaluation of an oral formulation using ion exchange resin as drug carrier.
2008
[Fluindione-induced acute generalised exanthematous pustulosis confirmed by patch testing].
2008 Apr
Colchicine: serious interactions.
2008 Aug
[Prospective study of oral anticoagulation control in 110 very elderly hospitalized patients and of risk factors for poor control].
2008 Dec
Analysis of indandione anticoagulant rodenticides in animal liver by eluent generator reagent free ion chromatography coupled with electrospray mass spectrometry.
2008 Dec 5
Development and evaluation of oral controlled release chlorpheniramine-ion exchange resinate suspension.
2008 Jul-Aug
Severe hemorrhagic syndrome due to similarity of drug names.
2008 Mar
Chemical substructures that enrich for biological activity.
2008 Nov 1
Comparison of INR stability between self-monitoring and standard laboratory method: preliminary results of a prospective study in 67 mechanical heart valve patients.
2008 Nov-Dec
Self-control of long-term oral anticoagulation using a point-of-care device.
2008 Nov-Dec
[Hepatic and renal toxicity to fluindione (Previscan)].
2008 Oct
[Acute interstitial nephritis of fluindione: about three cases].
2008 Oct
Evaluation of the palatability of three nonsteroidal antiinflammatory top-dress formulations in horses.
2008 Summer
Potentiometric determination of ionisation constants for diphacinone and chlorophacinone in a dioxane-water cosolvent system.
2009 Aug 15
Combinatorial mutasynthesis of scrambled beauvericins, cyclooligomer depsipeptide cell migration inhibitors from Beauveria bassiana.
2009 Jan 26
Formulation and optimization of sustained release tablets of venlafaxine resinates using response surface methodology.
2009 Jul
[Acute immuno-allergic interstitial nephritis after treatment with fluindione. Seven cases].
2009 Jul
A new VKORC1 mutation leading to an isolated resistance to fluindione.
2009 Jun
[Liver infarcts with early HELLP syndrome and probable catastrophic antiphospholipid syndrome].
2009 Mar
[Necrotizing folliculitis in Behçet's disease].
2009 Mar
[Multidrug intoxication].
2009 Mar-Apr
Budd-Chiari syndrome as a vascular complication of amebic liver abscess.
2009 Nov
[Inefficacy of vitamin K antagonists in an human immunodeficiency virus seropositive patient taking nevirapine].
2009 Nov
Conservative treatment of spontaneous and isolated dissection of mesenteric arteries.
2009 Nov-Dec
Use the INN to avoid confusion between drugs.
2009 Oct
[Severe overdose in vitamin K antagonist secondary to grapefruit juice absorption].
2009 Oct
Safety and efficacy of fondaparinux as an adjunctive treatment to thrombolysis in patients with high and intermediate risk pulmonary embolism.
2009 Oct
Effects of ion exchange resins in different mobile ion forms on semi-aerobic landfill leachate treatment.
2010
[Simultaneous determination of trace diphacinone and chlorophacinone in biological samples by high performance liquid chromatography coupled with ion trap mass spectrometry].
2010 Feb
[Thrombosis of the inferior vena cava revealing primary antiphospholipid syndrome: a case report].
2010 Feb
Formulation and evaluation of rizatriptan benzoate mouth disintegrating tablets.
2010 Jan
A novel prodrug strategy for beta-dicarbonyl carbon acids: syntheses and evaluation of the physicochemical characteristics of C-phosphoryloxymethyl (POM) and phosphoryloxymethyloxymethyl (POMOM) prodrug derivatives.
2010 Jun
Validation of a new liquid chromatography- tandem mass spectrometry ion-trap technique for the simultaneous determination of thirteen anticoagulant rodenticides, drugs, or natural products.
2010 Mar
[Glycopeptide-induced cutaneous adverse reaction].
2010 May
Acute toxicity of diphacinone in Northern bobwhite: effects on survival and blood clotting.
2010 Sep
Taste masking of Etoricoxib by using ion-exchange resin.
2010 Sep-Oct
Patents

Patents

Sample Use Guides

Initial: orally 200 mg in 2 equal doses on day 1, then 100 mg on day 2. Maintenance: 50-150 mg/day.
Route of Administration: Oral
In Vitro Use Guide
Experiments for determination of inhibition of vitamin-K-dependent carboxylation was determined using preparation of rat liver microsomes. Experimental reaction mixtures contained both vitamin K and a vitamin K antagonist. The control reaction mixture contained 3.00 ml of microsomal suspension, 0.81 ml of buffer II. 1.20 ml of an ATP-generating system, 0.60 ml of NADH (final concentration 2 mM), 0.30 ml of dithiothreitol (final concentration 7 m.V/) in buffer II. 0.060 ml of NaH[14C]O3 (1.0 uCi/uL added 0.5 min prior to reaction initiation) and at the time of reaction initiation 0.030 ml of vitamin K (final concentration 20 ug/ml) diluted in 0.85% sodium chloride solution. Reaction mixtures were equilibrated at 27 °C in a reciprocating shaker water bath at 100 excursions per minute. Serial samples (0.45 ml each) were collected from each control and blank reaction tube at 2,4, 6, 8, 10, 12, 14, 16, 30, 60, 90 and 120 min, and from each experimental reaction tube at 2,4, 6, 8, 10, 12, 14 and 16 min. Each sample was transferred to a tube containing I ml of ice-cold 10% TCA. Amount of product formed was determined using liquid scintillation spectrometer with the external standard method of quench correction. Phenindione inhibits Vitamin K-dependent carboxylation with IC50 of 19 uM.
Name Type Language
PHENINDIONE
HSDB   INN   MART.   MI   ORANGE BOOK   USP-RS   WHO-DD  
INN  
Official Name English
PHENINDIONE [MI]
Common Name English
PHENINDIONE [HSDB]
Common Name English
HEDULIN
Brand Name English
NSC-41693
Code English
1H-INDENE-1,3(2H)-DIONE, 2-PHENYL-
Systematic Name English
2-Phenyl-1,3-indandione
Systematic Name English
PHENINDIONE [ORANGE BOOK]
Common Name English
PHENINDIONE [MART.]
Common Name English
DANILONE
Brand Name English
phenindione [INN]
Common Name English
Phenindione [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-ATC B01AA02
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
WHO-VATC QB01AA02
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
NCI_THESAURUS C263
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
Code System Code Type Description
RXCUI
8130
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY RxNorm
NCI_THESAURUS
C66371
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
EVMPD
SUB09765MIG
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
WIKIPEDIA
PHENINDIONE
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
NSC
41693
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
MESH
D010630
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
ECHA (EC/EINECS)
201-454-4
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
DRUG BANK
DB00498
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
INN
23
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
SMS_ID
100000082255
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
CAS
83-12-5
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
ChEMBL
CHEMBL711
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
FDA UNII
5M7Y6274ZE
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
PUBCHEM
4760
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
HSDB
3155
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
DRUG CENTRAL
2130
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
EPA CompTox
DTXSID5023453
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
CHEBI
8066
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY
MERCK INDEX
m8618
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY Merck Index
IUPHAR
6838
Created by admin on Fri Dec 15 15:06:45 UTC 2023 , Edited by admin on Fri Dec 15 15:06:45 UTC 2023
PRIMARY