INDOBUFEN SODIUM

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H16NO3.Na
Molecular Weight	317.3143
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CCC(C([O-])=O)C1=CC=C(C=C1)N2CC3=CC=CC=C3C2=O

InChI

InChIKey=MEWDXXPKUBKKJO-UHFFFAOYSA-M

InChI=1S/C18H17NO3.Na/c1-2-15(18(21)22)12-7-9-14(10-8-12)19-11-13-5-3-4-6-16(13)17(19)20;/h3-10,15H,2,11H2,1H3,(H,21,22);/q;+1/p-1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1965501

Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme thereby suppressing thromboxane synthesis. Indobufen under brand name ibustrin is used in Italy for the following conditions: cerebrovascular insufficiency, atherosclerosis of peripheral and cerebral vessels, thrombophlebitis, deep vein thrombosis, and diabetes mellitus. In addition, this drug has been investigated in the phase II clinical trial for the prevention of thromboembolic events in patients with nonrheumatic atrial fibrillation. After oral administration, it is quickly and completely absorbed.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1965501	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Atrial fibrillation 131 Sources: https://clinicaltrials.gov/ct2/show/NCT00244426	Preventing	Phase III 665	Unknown Approved Use Unknown
Cerebrovascular insufficiency 15 Sources: http://www.sukl.eu/modules/medication/detail.php?code=0047845&tab=info	Preventing	Approved 8583	Ibustrin Approved Use Unknown
Thrombophlebitis 3 Sources: http://www.sukl.eu/modules/medication/detail.php?code=0047845&tab=info	Preventing	Approved 8583	Ibustrin Approved Use Unknown
Deep vein thrombosis 12 Sources: http://www.sukl.eu/modules/medication/detail.php?code=0047845&tab=info	Preventing	Approved 8583	Ibustrin Approved Use Unknown
Diabetes mellitus 93 Sources: http://www.sukl.eu/modules/medication/detail.php?code=0047845&tab=info	Palliative	Approved 8583	Ibustrin Approved Use Unknown

C_max

Value	Dose	Analyte	Population
23 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11370020/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	INDOBUFEN, (R)- serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
17.8 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11370020/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	INDOBUFEN, (S)- serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
32.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3733275/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	INDOBUFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.73 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1596290/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.93 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1596290/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
14.61 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/456404/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.24 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/456404/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Analyte	Population
2262 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11370020/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	INDOBUFEN, (R)- serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1309 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11370020/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	INDOBUFEN, (S)- serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
74.78 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/456404/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
64.67 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/456404/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
7.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11370020/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	INDOBUFEN, (R)- serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11370020/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	INDOBUFEN, (S)- serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3733275/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	INDOBUFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1596290/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1596290/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.63 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/456404/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.77 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/456404/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	INDOBUFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12237835/			INDOBUFEN serum	Homo sapiens

Doses

Dose	Population	Adverse events
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/	Other AEs: Stomach pain, Nausea... Other AEs: Stomach pain Nausea Vomiting Bleeding (0.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/

AEs

AE	Significance	Dose	Population
Nausea		400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/
Stomach pain		400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/
Vomiting		400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/
Bleeding	0.6%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9158644/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/107641#section=BioAssay-Results Page: 10.0	inconclusive [IC50 27.5404 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/107641#section=BioAssay-Results Page: 11.0	inconclusive [IC50 30.9008 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/107641#section=BioAssay-Results Page: 58.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/107641#section=BioAssay-Results Page: 9.0	yes [IC50 15.4871 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/107641#section=BioAssay-Results Page: 10.0	yes [IC50 21.8761 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/107641#section=BioAssay-Results Page: 63.0

PubMed

Title	Date	PubMed
Oral antiplatelet therapy in stroke prevention. Minireview.	2010-09	21048805
Antithrombotic therapy in cardiac embolism.	2010-08	21804782
A systematic review of clinical trials of pharmacological interventions for acute ischaemic stroke (1955-2008) that were completed, but not published in full.	2010-04-22	20412562
Emerging antiplatelet agents, differential pharmacology, and clinical utility.	2010	22282687
Modulatory effect of chiral nonsteroidal anti-inflammatory drugs on apoptosis of human neutrophils.	2008-02	18092300
Antiplatelet drugs in cardiological practice: established strategies and new developments.	2008	18827913
Clinical management of adult patients with a history of nonsteroidal anti-inflammatory drug-induced urticaria/angioedema: update.	2007-03-15	20525150
Upper gastrointestinal bleeding associated with antiplatelet drugs.	2006-01-15	16393302
Indobufen inhibits tissue factor in human monocytes through a thromboxane-mediated mechanism.	2006-01	16154551
[Recurrent hemoptysis following thienopyridines and amiodarone administration. therapeutic dilemma].	2005-08	16808316
Anticoagulants versus antiplatelet therapy for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attack.	2004-10-18	15494992
Atrial fibrillation and anticoagulation.	2004-10	16008178
Resolution of indobufen enantiomers by capillary zone electrophoresis. Pharmacokinetic studies of human serum.	2004-04-02	15065799
Endoscopic evaluation of the effects of indobufen and aspirin in healthy volunteers.	2004-03-05	14999361
[Stroke and Other Thromboembolic Complications of Atrial Fibrillation. Part III. Prevention With Other Antithrombotic Agents.].	2004	15477780
Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population [ISRCTN89345269].	2003-08-26	12939169
Protein binding of indobufen enantiomers: pharmacokinetics of free fraction-studies after single or multiple doses of rac-indobufen.	2002-10	12237835
Thromboembolic complications after total hip replacement.	2002	11954849
[Thromboembolism in non-rheumatic atrial fibrillation].	2001-09	11759619
[Guidelines for antithrombotic therapy in atrial fibrillation: what the Italian Hemostasis and Thrombosis Society thinks].	2001-09	11759618
Long term anticoagulation or antiplatelet treatment. Drug name was incorrect.	2001-07-28	11496889
Steady-state pharmacokinetics of indobufen enantiomers in patients with obliterative atherosclerosis.	2001-06	11370020
Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation.	2001-02-10	11159653
Indobufen: an updated review of its use in the management of atherothrombosis.	2001	11392445
A randomized trial comparing ticlopidine hydrochloride with indobufen for the prevention of stroke in high-risk patients (TISS Study). Ticlopidine Indobufen Stroke Study.	1997-01-01	9127122

Sample Use Guides

In Vivo Use Guide

indobufen capsules 100 and 200 mg

Route of Administration: Oral

In Vitro Use Guide

At low concentrations (10 microM), indobufen completely inhibited secondary platelet aggregation, the release reaction and TxB2 production stimulated by ADP, epinephrine and low concentrations of platelet-activating factor (PAF acether). Higher concentrations of indobufen (100 microM) completely inhibited TxB2 production, platelet aggregation and ATP release induced by arachidonic acid (1 mM) or collagen (2 micrograms/ml). The inhibitory effect was partially overcome by higher concentrations of arachidonic acid (2 mM).

Name

Type

Language

(±)-2-(P-(1-OXO-2-ISOINDOLINYL)PHENYL)BUTYRIC ACID, SODIUM SALT

Preferred Name

English

INDOBUFEN SODIUM

Common Name

English

BENZENEACETIC ACID, 4-(1,3-DIHYDRO-1-OXO-2H-ISOINDOL-2-YL)-.ALPHA.-ETHYL-, SODIUM SALT (1:1)

Common Name

English

Indobufen sodium [WHO-DD]

Common Name

English

BENZENEACETIC ACID, 4-(1,3-DIHYDRO-1-OXO-2H-ISOINDOL-2-YL)-.ALPHA.-ETHYL-, SODIUM SALT

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C257