IBUDILAST

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H18N2O
Molecular Weight	230.3055
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C

InChI

InChIKey=ZJVFLBOZORBYFE-UHFFFAOYSA-N

InChI=1S/C14H18N2O/c1-9(2)13-12(14(17)10(3)4)11-7-5-6-8-16(11)15-13/h5-10H,1-4H3

HIDE SMILES / InChI

Description

Ibudilast (KETAS®) is a non-selective cyclic nucleotide phosphodiesterase (PDE) inhibitor. It is an antithrombotic, antiasthmatic drug that is used for improving prognosis and relieving symptoms in patients suffering from ischemic stroke and for the treatment of bronchial asthma. A definitive mechanism of its action is yet to be established. However, inhibition of the release of inflammatory cytokines, inhibition of leukocyte activation, and inhibition of the expression of cell adhesion molecules have been proposed as likely mechanisms of action of ibudilast (KETAS®). It is currently in development in the US (for instance as a potential therapy for multiple sclerosis), but is approved for use in Japan.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Phosphodiesterase 3A 7	Inhibitor 8,504	9.5 µM [Ki]
Phosphodiesterase 4A 13	Inhibitor 8,504	3.3 µM [Ki]
Phosphodiesterase 10A 13	Inhibitor 8,504	1.27 µM [Ki]
Phosphodiesterase 11A 3	Inhibitor 8,504	8.9 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Bronchial asthma 50	Primary		Approved 8,583	KETAS
Cerebral infarction 14	Palliative		Approved 8,583	KETAS

C_max

Value	Dose	Analyte	Population
32 ng/mL	30 mg single, oral	IBUDILAST plasma	Homo sapiens
59.9 ng/mL	30 mg 2 times / day steady-state, oral	IBUDILAST plasma	Homo sapiens
59.9 ng/mL	30 mg 2 times / day steady-state, oral	IBUDILAST plasma	Homo sapiens
25 ng/mL	10 mg single, oral	IBUDILAST blood	Homo sapiens
30 ng/mL	10 mg 3 times / day steady-state, oral	IBUDILAST blood	Homo sapiens
12.9 ng/mL	10 mg single, oral	IBUDILAST serum	Homo sapiens

AUC

Value	Dose	Analyte	Population
373 ng × h/mL	30 mg single, oral	IBUDILAST plasma	Homo sapiens
517 ng × h/mL	30 mg 2 times / day steady-state, oral	IBUDILAST plasma	Homo sapiens
507 ng × h/mL	30 mg 2 times / day steady-state, oral	IBUDILAST plasma	Homo sapiens
334 ng × h/mL	10 mg single, oral	IBUDILAST blood	Homo sapiens
118.44 ng × h/mL	10 mg single, oral	IBUDILAST serum	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
19.2 h	30 mg single, oral	IBUDILAST plasma	Homo sapiens
12 h	10 mg single, oral	IBUDILAST blood	Homo sapiens
7.76 h	10 mg single, oral	IBUDILAST serum	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
3%			IBUDILAST serum	Homo sapiens
0.5%			IBUDILAST plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
100 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT	Other AEs: Abdominal pain, Diarrhea...
30 mg 2 times / day multiple, oral Studied dose	healthy, ADULT	Disc. AE: Vomiting...

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AEs

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AE	Significance	Dose	Population
Skin infection	1%	100 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Upper respiratory tract infection	10%	100 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Fatigue	11%	100 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Insomnia	11%	100 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT
Diarrhea	16%	100 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT

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PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

In case of bronchhial asthma: The usual adult dosage for oral use is 10 mg of ibudulast (KETAS®) twice daily. In case of cerebro-vascular disorders: The usual dosage for oral use is 10 mg of ibudulast (KETAS®) three times daily. The dosage may be adjusted according to the patient's symptoms.

Route of Administration: Oral

In Vitro Use Guide

The inhibitory effect of ibudilast against the human phosphodiesterase (PDE) enzyme family was measured. Ibudilast did not exhibit PDE4 subfamily selectivity with Ki values ranging from 3.3 uM to 6.3 uM. Inhibition of PDE10 by ibudilast was essentially the same with cAMP and cGMP as substrates yielding Ki values of 2.2 uM and 1.3 uM, respectively. PDE11 was tested for inhibition using both cAMP and cGMP substrates and cAMP hydrolysis was sensitive to inhibition with a Ki value of 8.9 uM. PDE3A was inhibited by ibudilast with a Ki of 9.5 uM.

Show entries

Name

Type

Language

KETAS

Preferred Name

English

IBUDILAST

Official Name

English

AV-411

Code

English

IBUDILAST [MART.]

Common Name

English

AV411

Code

English

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Classification Tree

Code System

Code

Leukotriene receptor antagonists

WHO-VATC

QR03DC04

Leukotriene receptor antagonists

WHO-ATC

R03DC04

Designated

FDA ORPHAN DRUG

889222

Positive

EU-Orphan Drug

EU/3/16/1801

Agent Affecting Cardiovascular System

NCI_THESAURUS

C29707

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Code System

Code

Type

Description

FDA UNII

M0TTH61XC5

PRIMARY

CAS

50847-11-5

PRIMARY

DRUG BANK

DB05266

PRIMARY

IUPHAR

7399

PRIMARY

INN

6068

PRIMARY

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ACTIVE MOIETY


					M0TTH61XC5

IBUDILAST

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound