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
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.	2010-10-12	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).	2010-09-11	21587397
Doxofylline: a "novofylline".	2010-08	20380886
Spectrophotometric and reversed-phase high-performance liquid chromatographic method for the determination of doxophylline in pharmaceutical formulations.	2010-07	21042488
[Effects of tetramethylpyrazine on fractalkine and tumor necrosis factor-alpha expression in patients with chronic pulmonary heart disease].	2010-04	20669672
[Meta-analysis of efficacy and safety of oral theophylline in chronic obstructive pulmonary disease].	2010-03-02	20367966
Doxofylline: a promising methylxanthine derivative for the treatment of asthma and chronic obstructive pulmonary disease.	2009-10	19678793
Treatment of moderate chronic obstructive pulmonary disease (stable) with doxofylline compared with slow release theophylline--a multicentre trial.	2008-12	19370950
[Determination of levosimendan and its main metabolites in human plasma with HPLC-MS/MS method].	2008-10	19127871
Preparation and bioavailability of sustained-release doxofylline pellets in beagle dogs.	2008-07	18608467
Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of doxofylline in human serum: application to a clinical pharmacokinetic study.	2008-06	18254143
Doxofylline: The next generation methylxanthine.	2008-03	18376093
Doxofyllinium tetra-chloridoanti-monate(III) monohydrate.	2007-12-12	21200515
Therapeutic potential of adenosine receptor antagonists and agonists.	2007-08	20144084
[Effect of doxofylline on calcium-activated potassium channels in human peripheral blood eosinophils in asthma].	2005-12	16409781
[Clinical study on doxofylline injection in treatment of children with acute asthma attacks].	2004-02	15059495
Methylxanthines for exacerbations of chronic obstructive pulmonary disease: meta-analysis of randomised trials.	2003-09-20	14500434
Conclusion without support - remarks on 'Efficacy and safely of doxyphyllin compared to Theophylline in chronic reversible asthma- a double-blind randomized placebo-controlled multicentre trial' by Goldstein MF, Chervinsky P (published in MedSciMonit, 2002; 8(4):CR297-304.	2002-08	12229856
Efficacy and safety of doxofylline compared to theophylline in chronic reversible asthma -- a double-blind randomized placebo-controlled multicentre clinical trial.	2002-04	11951074
Methyl-xanthines for exacerbations of chronic obstructive pulmonary disease.	2001	11279755
Doxofylline: a new generation xanthine bronchodilator devoid of major cardiovascular adverse effects.	2001	11268710
Doxofylline and respiratory mechanics. Short-term effects in mechanically ventilated patients with airflow obstruction and respiratory failure.	1989-10	2791671
Doxofylline, an antiasthmatic drug lacking affinity for adenosine receptors.	1988-09-01	3245738

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

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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