DOXOFYLLINE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H14N4O4
Molecular Weight	266.2533
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C2=C(N(CC3OCCO3)C=N2)C(=O)N(C)C1=O

InChI

InChIKey=HWXIGFIVGWUZAO-UHFFFAOYSA-N

InChI=1S/C11H14N4O4/c1-13-9-8(10(16)14(2)11(13)17)15(6-12-9)5-7-18-3-4-19-7/h6-7H,3-5H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C11H14N4O4
Molecular Weight	266.2533
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=11268710
Curator's Comment: description was created based on several sources, including http://cathaydrug.ph/product/dilatair/ https://www.ncbi.nlm.nih.gov/pubmed/18376093

Doxofylline (7-(1, 3-dioxalan-2-ylmethyl) theophylline) is a novel xanthine bronchodilator which differs from theophylline in that it contains a dioxalane group in position 7. Doxofylline is indicated for the treatment of bronchial asthma, pulmonary disease with spastic bronchial component and Chronic Obstructive Pulmonary Disease (COPD). Doxofylline does not directly inhibit any of the known HDAC enzymes, and did not inhibit any phosphodiesterase (PDE) enzyme sub types or act as an antagonist at any of the known adenosine receptors, except for PDE2A(1), and adenosine A(2A) and only at the highest tested concentration (10(-4) M). Doxofylline has greatly decreased affinity towards adenosine A1 and A2 receptors, which explain its better safety profile. Moreover, it does not interfere with calcium influx into the cells nor antagonize calcium channel blockers. Doxofylline has been shown to be a more potent bronchodilator with fewer side effects than theophylline. This drug should not be administered together with other xanthine derivatives, including beverages and foods containing caffeine.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 2A 7 Target ID: CHEMBL2652 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22138191	Inhibitor 8504
Adenosine A2a receptor 31 Target ID: CHEMBL251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22138191	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Bronchial asthma 50 Sources: http://cathaydrug.ph/product/dilatair/	Palliative		Approved 8583	Dilatair Approved Use Unknown
Chronic obstructive pulmonary disease 175 Sources: http://cathaydrug.ph/product/dilatair/	Palliative		Approved 8583	Ddilatair Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31181483/	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:		DOXOFYLLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1687 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18254143/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		DOXOFYLLINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1.76 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31181483/	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:		DOXOFYLLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4814 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18254143/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		DOXOFYLLINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31181483/	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:		DOXOFYLLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.32 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18254143/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		DOXOFYLLINE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
7.4% EXPERIMENT http://wprim.whocc.org.cn/admin/article/articleDetail?WPRIMID=557546&articleId=557546			DOXOFYLLINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
400 mg 3 times / day multiple, oral Recommended Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31884206/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31884206/	Disc. AE: Headache, Insomnia... Other AEs: Nausea... AEs leading to discontinuation/dose reduction: Headache Insomnia Other AEs: Nausea Sources: https://pubmed.ncbi.nlm.nih.gov/31884206/

AEs

AE	Significance	Dose	Population
Nausea		400 mg 3 times / day multiple, oral Recommended Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31884206/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31884206/
Headache	Disc. AE	400 mg 3 times / day multiple, oral Recommended Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31884206/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31884206/
Insomnia	Disc. AE	400 mg 3 times / day multiple, oral Recommended Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31884206/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31884206/

PubMed

Title	Date	PubMed
Doxofylline, an antiasthmatic drug lacking affinity for adenosine receptors.	1988 Sep-Oct	3245738
Doxofylline and respiratory mechanics. Short-term effects in mechanically ventilated patients with airflow obstruction and respiratory failure.	1989 Oct	2791671
Doxofylline: a new generation xanthine bronchodilator devoid of major cardiovascular adverse effects.	2001	11268710
Therapeutic potential of adenosine receptor antagonists and agonists.	2007 Aug	20144084
Doxofyllinium tetra-chloridoanti-monate(III) monohydrate.	2007 Dec 12	21200515
Treatment of moderate chronic obstructive pulmonary disease (stable) with doxofylline compared with slow release theophylline--a multicentre trial.	2008 Dec	19370950
[Determination of levosimendan and its main metabolites in human plasma with HPLC-MS/MS method].	2008 Oct	19127871
Doxofylline: a promising methylxanthine derivative for the treatment of asthma and chronic obstructive pulmonary disease.	2009 Oct	19678793
[Effects of tetramethylpyrazine on fractalkine and tumor necrosis factor-alpha expression in patients with chronic pulmonary heart disease].	2010 Apr	20669672
Doxofylline: a "novofylline".	2010 Aug	20380886
Spectrophotometric and reversed-phase high-performance liquid chromatographic method for the determination of doxophylline in pharmaceutical formulations.	2010 Jul	21042488
[Meta-analysis of efficacy and safety of oral theophylline in chronic obstructive pulmonary disease].	2010 Mar 2	20367966
A randomized, open labeled, comparative study to assess the efficacy and safety of controller medications as add on to inhaled corticosteroid and long-acting β2 agonist in the treatment of moderate-to-severe persistent asthma.	2010 Oct-Dec	20935397
7-(1,3-Dioxolan-2-ylmethyl)-1,3-di-methyl-2,6-dioxo-2,3,6,7-tetra-hydro-1H-purin-9-ium tetra-chloridoferrate(III).	2010 Sep 11	21587397

Patents

Sample Use Guides

In Vivo Use Guide

Elderly Patients: 200 mg tablet two or three times daily. Adults: 400 mg tablet two or three times daily.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:25:58 GMT 2025` Edited by `admin` on `Mon Mar 31 19:25:58 GMT 2025`
Record UNII	MPM23GMO7Z
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DOXOFYLLINE

Official Name

English

ABC 12/3

Preferred Name

English

NSC-759645

Code

English

1H-PURINE-2,6-DIONE, 7-(1,3-DIOXOLAN-2-YLMETHYL)-3,7-DIHYDRO-1,3-DIMETHYL-

Systematic Name

English

DOXOFYLLINE [MART.]

Common Name

English

ANSIMAR

Common Name

English

DOXOFYLLINE [MI]

Common Name

English

DIOXYFILLINE

Common Name

English

DOXOFYLLINE [USAN]

Common Name

English

DOXOPHYLLINE

Common Name

English

doxofylline [INN]

Common Name

English

VENTAX

Common Name

English

ABC-12/3

Code

English

Doxofylline [WHO-DD]

Common Name

English

7-(1,3-Dioxolan-2-ylmethyl)theophylline

Systematic Name

English

SYNASMA

Common Name

English

Classification Tree Code System Code

WHO-VATC

QR03DA11