DYPHYLLINE

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C10H14N4O4
Molecular Weight	254.243
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cn1c2c(c(=O)n(C)c1=O)n(CC(CO)O)cn2

InChI

InChIKey=KSCFJBIXMNOVSH-UHFFFAOYSA-N

InChI=1S/C10H14N4O4/c1-12-8-7(9(17)13(2)10(12)18)14(5-11-8)3-6(16)4-15/h5-6,15-16H,3-4H2,1-2H3

HIDE SMILES / InChI

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=136395

Dyphylline is 7-(2,3-dihydroxypropyl)-theophylline, a white, extremely bitter, amorphous powder that is freely soluble in water and soluble in alcohol. Dyphylline is stable in gastrointestinal fluids over a wide range of pH. Dyphylline is a xanthine derivative with pharmacologic actions similar to theophylline and other members of this class of drugs. Its primary action is that of bronchodilation, but it also exhibits peripheral vasodilatory and other smooth muscle relaxant activity to a lesser degree. The bronchodilatory action of dyphylline, as with other xanthines, is thought to be mediated through competitive inhibition of phosphodiesterase with a resulting increase in cyclic AMP producing relaxation of the bronchial smooth muscle. Dyphylline exerts its bronchodilatory effects directly and, unlike theophylline, is excreted unchanged by the kidneys without being metabolized by the liver. Because of this, dyphylline pharmacokinetics and plasma levels are not influenced by various factors that affect liver function and hepatic enzyme activity, such as smoking, age, congestive heart failure, or concomitant use of drugs which affect liver function.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
cAMP signaling pathway 8 Target ID: map04024 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1545351	Inhibitor 7701	Acute bronchial asthma Chronic bronchitis Emphysema

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute bronchial asthma 1 Sources: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=136395	Primary	cAMP signaling pathway	Approved 7997	NEOTHYLLINE Approved Use Indications and Usage For relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema. Launch Date -594000000000
Chronic bronchitis 48 Sources: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=136395	Primary	cAMP signaling pathway	Approved 7997	NEOTHYLLINE Approved Use Indications and Usage For relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema. Launch Date -594000000000
Emphysema 13 Sources: https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=136395	Primary	cAMP signaling pathway	Approved 7997	NEOTHYLLINE Approved Use Indications and Usage For relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema. Launch Date -594000000000

C_max

Value	Dose	Co-administered	Analyte	Population
8.21 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/4009445	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		DYPHYLLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
20.16 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/4009445	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		DYPHYLLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.13 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/4009445	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		DYPHYLLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
5 mg/kg single, intragluteal Dose: 5 mg/kg Route: intragluteal Route: single Dose: 5 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7309903/	healthy, 20 - 35 years Health Status: healthy Age Group: 20 - 35 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/7309903/	Sources: https://pubmed.ncbi.nlm.nih.gov/7309903/
250 mg single, respiratory Dose: 250 mg Route: respiratory Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/	Other AEs: Bronchospasm... Other AEs: Bronchospasm (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/
375 mg single, respiratory Dose: 375 mg Route: respiratory Route: single Dose: 375 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/	Other AEs: Bronchospasm... Other AEs: Bronchospasm (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/

AEs

AE	Significance	Dose	Population
Bronchospasm	2 patients	250 mg single, respiratory Dose: 250 mg Route: respiratory Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/
Bronchospasm	2 patients	375 mg single, respiratory Dose: 375 mg Route: respiratory Route: single Dose: 375 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/6957527/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 574

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 639	inhibitor 2614 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286305/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4728	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4728
MolPort	MolPort-001-783-701	https://www.molport.com/shop/molecule-link/MolPort-001-783-701

PubMed

Title	Date	PubMed
Multi-component kinetic-spectrophotometric analysis. Selection of wavelength and time ranges.	2001 Jul	11478649
Application of micellar electrokinetic chromatography to the quality control of a pharmaceutical preparation containing three bronchodilators.	2002 Feb	11870768
Electrophoretic behaviour of pharmacologically active alkylxanthines.	2002 Mar 15	11991004
Kinetic-spectrophotometric determination of theophylline, dyphylline, and proxyphylline by use of partial least-squares regression.	2002 Sep	12207237
Wet granulation fine particle ethylcellulose tablets: effect of production variables and mathematical modeling of drug release.	2003	12866940
Simultaneous determination of theophylline and dyphylline by micellar electrokinetic chromatography and application in drug formulations.	2003 Oct 5	14522037
Modeling of drug release from partially coated matrices made of a high viscosity HPMC.	2004 May 19	15113619
Optimization and characterization of controlled release multi-particulate beads coated with starch acetate.	2005 Apr 27	15814233
HPLC and chemometric assisted spectrophotometric methods for simultaneous determination of diprophylline, phenobarbitone and papaverine hydrochloride.	2005 Sep	16023119
[Clinical observation on shufei granule in improving right ventricular function of patients with chronic pulmonary heart disease].	2006 Aug	16970099
Rapid determination of acyclovir in plasma and cerebrospinal fluid by micellar electrokinetic chromatography with direct sample injection and its clinical application.	2006 Feb	16411274
Extruded and spheronized beads containing Carbopol 974P to deliver nonelectrolytes and salts of weakly basic drugs.	2006 Sep 14	16828248
[Combining LABA and ICS in patients with severe COPD].	2007 Jan-Feb	17642199
Hydroxypropyl methylcellulose acetate succinate: potential drug-excipient incompatibility.	2008	18758966
A comparison of the stability of ertapenem and meropenem in pharmaceutical preparations in solid state.	2008 Jan 7	17936535
New validated liquid chromatographic and chemometrics-assisted UV spectroscopic methods for the determination of two multicomponent cough mixtures in syrup.	2008 Jan-Feb	18376584
Synthesis and activity against HBV of novel Tetra-seconucleoside analogues of dyphlline having the acyclic chains of ACV and HBG.	2008 Mar	18260013
Synthesis, pharmacological activity and nitric oxide generation by nitrate derivatives of theophylline.	2008 May	18416941
Expression and purification of human mPGES-1 in E. coli and identification of inhibitory compounds from a drug-library.	2008 Nov 30	19017494
Accuracy of Veterans Affairs databases for diagnoses of chronic diseases.	2009 Oct	19755002
Validation of Raman spectroscopic procedures in agreement with ICH guideline Q2 with considering the transfer to real time monitoring of an active coating process.	2010 Dec 1	20638213
Feasibility of Raman spectroscopy as PAT tool in active coating.	2010 Feb	19778159
Screening-based discovery of drug-like O-GlcNAcase inhibitor scaffolds.	2010 Feb 19	20026047
Modeling drug release from PVAc/PVP matrix tablets.	2010 Jan 25	19737588
Spectrophotometric and reversed-phase high-performance liquid chromatographic method for the determination of doxophylline in pharmaceutical formulations.	2010 Jul	21042488

Patents

Sample Use Guides

In Vivo Use Guide

Usual adult dosage: Up to 15 mg/kg every six hours. Dosage should be individually titrated according to the severity of the condition and the response of the patient. Appropriate dosage adjustments should be made in patients with impaired renal function

Route of Administration: Oral

In Vitro Use Guide

Human acute T-lymphocytic leukemia cells CEM-GH (CEM) were cultured with Dyphylline (10 -1000 mkg/mL) for 4 days, and MTT assay measurements are expressed as a viability ratio of drug-treated cells to untreated control cells in each experiment. Dyphylline suppress the growth of human CEM ALL cells in culture with EC50~100 mkg/mL.

Name

Type

Language

DYPHYLLINE

Official Name

English

DIPROPHYLLINE [WHO-DD]

Common Name

English

DIPROPHYLLINE [INN]

Common Name

English

DYPHYLLINE [ORANGE BOOK]

Common Name

English

DYPHYLLINE [HSDB]

Common Name

English

1H-PURINE-2,6-DIONE, 7-(2,3-DIHYDROXYPROPYL)-3,7-DIHYDRO-1,3-DIMETHYL-, (+/-)-

Systematic Name

English

DIPROPHYLLINE [EP MONOGRAPH]

Common Name

English

NSC-14305

Code

English

DYPHILLINE

Common Name

English

DILOR

Brand Name

English

DYPHYLLINE [USP-RS]

Common Name

English

DIPROPHYLLINE

Official Name

English

NEOTHYLLINE

Brand Name

English

DIPROPHYLLINE [JAN]

Common Name

English

DYPHYLLINE [USP MONOGRAPH]

Common Name

English

DYPHYLLINE [INCI]

Common Name

English

(+/-)-7-(2,3-DIHYDROXYPROPYL)THEOPHYLLINE

Systematic Name

English

DYPHYLLINE [VANDF]

Common Name

English

LUFYLLIN

Brand Name

English

DYPHYLLINE [MI]

Common Name

English

DIPROPHYLLINE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C744