U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C13H18N4O3
Molecular Weight 278.307
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PENTOXIFYLLINE

SMILES

CN1C=NC2=C1C(=O)N(CCCCC(C)=O)C(=O)N2C

InChI

InChIKey=BYPFEZZEUUWMEJ-UHFFFAOYSA-N
InChI=1S/C13H18N4O3/c1-9(18)6-4-5-7-17-12(19)10-11(14-8-15(10)2)16(3)13(17)20/h8H,4-7H2,1-3H3

HIDE SMILES / InChI

Molecular Formula C13H18N4O3
Molecular Weight 278.307
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Pentoxil (Pentoxifylline Extended-release Tablets, USP) is indicated for the treatment of patients with intermittent claudication based on chronic occlusive arterial disease of the limbs. Pentoxil can improve function and symptoms but is not intended to replace more definitive therapy, such as surgical bypass, or removal of arterial obstructions when treating peripheral vascular disease. Pentoxifylline and its metabolites improve the flow properties of blood by decreasing its viscosity. In patients with chronic peripheral arterial disease, this increases blood flow to the affected microcirculation and enhances tissue oxygenation. The precise mode of action of pentoxifylline and the sequence of events leading to clinical improvement are still to be defined. Pentoxifylline inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, pentoxifylline also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity. It is also a non-selective adenosine receptor antagonist. Pentoxifylline administration has been shown to produce dose-related hemorrheologic effects, lowering blood viscosity, and improving erythrocyte flexibility. Pentoxifylline has been shown to increase leukocyte deformability and to inhibit neutrophil adhesion and activation. Tissue oxygen levels have been shown to be significantly increased by therapeutic doses of pentoxifylline in patients with peripheral arterial disease. Clinical trials were conducted using either extended-release pentoxifylline tablets for up to 60 weeks or immediate-release pentoxifylline capsules for up to 24 weeks. Dosage ranges in the tablet studies were 400 mg bid to tid and in the capsule studies, 200-400 mg tid. The incidence of adverse reactions was higher in the capsule studies (where dose related increases were seen in digestive and nervous system side effects) than in the tablet studies. Studies with the capsule include domestic experience, whereas studies with the extended-release tablets were conducted outside the U.S.

CNS Activity

Curator's Comment: Pentoxifylline readily crosses the blood-brain barrier, so systemically administered drug might reduce both circulating and brain levels of pro-inflammatory cytokines

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PENTOXIL

Approved Use

INDICATIONS & USAGE Pentoxifylline extended-release tablets are indicated for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. Pentoxifylline can improve function and symptoms but is not intended to replace more definitive therapy, such as surgical bypass, or removal of arterial obstructions when treating peripheral vascular disease.

Launch Date

1999
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1607 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
272 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
683 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
719 ng/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1228 ng × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
193 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
380 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
4842 ng × h/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.84 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
0.48 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0.39 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENTOXIFYLLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
unhealthy, adult and children
n = 44
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: adult and children
Sex: unknown
Population Size: 44
Sources:
Disc. AE: Flushing, Hypotension...
AEs leading to
discontinuation/dose reduction:
Flushing (44 patients)
Hypotension (44 patients)
Convulsions (44 patients)
Somnolence (44 patients)
Loss of consciousness (44 patients)
Fever (44 patients)
Agitation (44 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Agitation 44 patients
Disc. AE
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
unhealthy, adult and children
n = 44
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: adult and children
Sex: unknown
Population Size: 44
Sources:
Convulsions 44 patients
Disc. AE
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
unhealthy, adult and children
n = 44
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: adult and children
Sex: unknown
Population Size: 44
Sources:
Fever 44 patients
Disc. AE
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
unhealthy, adult and children
n = 44
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: adult and children
Sex: unknown
Population Size: 44
Sources:
Flushing 44 patients
Disc. AE
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
unhealthy, adult and children
n = 44
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: adult and children
Sex: unknown
Population Size: 44
Sources:
Hypotension 44 patients
Disc. AE
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
unhealthy, adult and children
n = 44
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: adult and children
Sex: unknown
Population Size: 44
Sources:
Loss of consciousness 44 patients
Disc. AE
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
unhealthy, adult and children
n = 44
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: adult and children
Sex: unknown
Population Size: 44
Sources:
Somnolence 44 patients
Disc. AE
80 mg/kg single, oral
Overdose
Dose: 80 mg/kg
Route: oral
Route: single
Dose: 80 mg/kg
Sources:
unhealthy, adult and children
n = 44
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: adult and children
Sex: unknown
Population Size: 44
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
likely (co-administration study)
Comment: Concomitant administration of strong CYP1A2 inhibitors (including e.g. ciprofloxacin or fluvoxamine) may increase the exposure to pentoxifylline
Page: 7.0
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Indobufen: an updated review of its use in the management of atherothrombosis.
2001
Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology.
2001
Cilostazol: a novel treatment option in intermittent claudication.
2001 Apr
Successful combination therapy--flunarizine, pentoxifylline, and cholestyramine--for spur cell anemia.
2001 Apr
A new treatment for peripheral arterial disease.
2001 Apr
Value of the hamster oocyte test and computerised measurements of sperm motility in predicting if four or more viable embryos will be obtained in an IVF cycle.
2001 Apr
Acute stroke management in the local general hospital.
2001 Apr
Intracellular pool of IL-10 receptors in specific granules of human neutrophils: differential mobilization by proinflammatory mediators.
2001 Apr 15
A pilot study of pentoxifylline in the treatment of radiation-induced trismus.
2001 Aug
The effect of pentoxifylline on intestinal ischemia/reperfusion injury.
2001 Feb
Pentoxifylline treatment of mice with chronic pulmonary tuberculosis accelerates the development of destructive pathology.
2001 Feb
Inhibition of matrix metalloproteinases enhances breaking strength of colonic anastomoses in an experimental model.
2001 Feb
Progressive hearing loss in hearing impaired children: immediate results of antiphlogistic--rheologic infusion therapy.
2001 Feb
May pentoxifylline improve lung function after one-lung flooding?
2001 Jan
Bleomycin-induced lung toxicity and pentoxifylline.
2001 Jan 15
Crux medicorum ulcerated radiation-induced fibrosis - successful therapy with pentoxifylline and vitamin E.
2001 Jan-Feb
Intravenous pentoxifylline does not enhance the pulmonary haemodynamic efficacy of frusemide in strenuously exercising thoroughbred horses.
2001 Jul
Pentoxifylline improves in vitro fertilization and subsequent development of bovine oocytes.
2001 Jul 15
A redox-regulated tyrosine phosphorylation cascade in rat spermatozoa.
2001 Jul-Aug
Pentoxifylline effects on acute and late complications after radiotherapy in rabbit.
2001 Jun
Therapeutic effects of Vascupump treatment patients with Fontaine Stage II B arteriopathy.
2001 Jun
Comparative effects of cilostazol and other therapies for intermittent claudication.
2001 Jun 28
[Acute alcoholic hepatitis: treatments].
2001 Jun 9
Inhibition of human CYP1A2 activity in vitro by methylxanthines: potent competitive inhibition by 8-phenyltheophylline.
2001 Mar
[The effect of pentoxifylline on the deformability of erythrocytes in erythrocyte concentrates in additive solution].
2001 Mar
Necrobiosis lipoidica. Indolent plaques may signal diabetes.
2001 Mar
Enhancement of bone morphogenetic protein-2-induced new bone formation in mice by the phosphodiesterase inhibitor pentoxifylline.
2001 Mar
Treatment of intermittent claudication with pentoxifylline and cilostazol.
2001 Mar 15
An easy producible new oral hydrocolloid drug delivery system with a late burst in the release profile.
2001 Mar 23
Pentoxifylline inhibits the synthesis and IFN-gamma-inducing activity of IL-18.
2001 May
Preventive effect of inhaled nitric oxide and pentoxifylline on ischemia/reperfusion injury after lung transplantation.
2001 May 15
Pentoxifylline: wonder drug?
2001 May-Jun
Patents

Sample Use Guides

The usual dosage of Pentoxil (Pentoxifylline Extended-release Tablets, USP) in extended-release tablet form is one tablet (400 mg) three times a day with meals. While the effect of Pentoxil may be seen within 2 to 4 weeks, it is recommended that treatment be continued for at least 8 weeks. Efficacy has been demonstrated in double-blind clinical studies of 6 months duration.
Route of Administration: Oral
The proliferation rate of the cells treated with 1 mM Pentoxifylline (PTX) significantly decreased compared with that of the control in T6 cells (78.3 ± 6.03% at 12 h, 61.0 ± 7.55% at 24 h, and 44.7 ± 2.08% at 48 h, p < 0.05). PTX (1 mM) also decreased the fraction of the hepatic stellate cells (HSC) population in the S and G2/M-phases of the cell cycle in primary activated rat HSCs. The Raf-1 inhibitor GW5074 and the ERK inhibitor U0126 had inhibitory effects that were similar to those of PTX on HSC proliferation. In addition, PTX inhibited the phosphorylation of Raf-1 (p-Raf-1) and ERK (p-ERK) in a dose- and time-dependent manner in HSCs.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:33:57 GMT 2023
Edited
by admin
on Fri Dec 15 15:33:57 GMT 2023
Record UNII
SD6QCT3TSU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PENTOXIFYLLINE
EP   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
PENTOXIFYLLINE [ORANGE BOOK]
Common Name English
PENTOXIFYLLINE [MART.]
Common Name English
NSC-637086
Code English
OXYPENTIFYLLINE
Common Name English
BL-191
Code English
TRENTAL
Brand Name English
PENTOXIFYLLINE [EP MONOGRAPH]
Common Name English
PENTOXIFYLLINE [VANDF]
Common Name English
PENTOXIFYLLINE [JAN]
Common Name English
PENTOXIL
Brand Name English
PENTOXIFYLLINE [USP-RS]
Common Name English
pentoxifylline [INN]
Common Name English
C04AD03
Code English
1H-PURINE-2,6-DIONE, 3,7-DIHYDRO-3,7-DIMETHYL-1-(5-OXOHEXYL)-
Systematic Name English
NSC-758481
Code English
PENTOXIPHYLLIN
Common Name English
PENTOXIFYLLINE [USP MONOGRAPH]
Common Name English
Pentoxifylline [WHO-DD]
Common Name English
PENTOXIFYLLINE [MI]
Common Name English
BL 191
Code English
1-(5-Oxohexyl)theobromine
Systematic Name English
PENTOXIFYLLINE [USAN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 369712
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
WHO-VATC QC04AD03
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
NDF-RT N0000009065
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
NCI_THESAURUS C744
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
NCI_THESAURUS C1327
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
NCI_THESAURUS C221
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
LIVERTOX NBK548672
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
NDF-RT N0000175895
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
WHO-ATC C04AD03
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
Code System Code Type Description
NSC
637086
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY
INN
3309
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
LACTMED
Pentoxifylline
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
DAILYMED
SD6QCT3TSU
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
FDA UNII
SD6QCT3TSU
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
RS_ITEM_NUM
1508901
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY
MERCK INDEX
m8519
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY Merck Index
NSC
758481
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY
MESH
D010431
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY
CAS
6493-05-6
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
EVMPD
SUB09705MIG
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
PUBCHEM
4740
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY
RXCUI
8013
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY RxNorm
DRUG CENTRAL
2099
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
DRUG BANK
DB00806
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
IUPHAR
7095
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
ChEMBL
CHEMBL628
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
EPA CompTox
DTXSID7023437
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
NCI_THESAURUS
C733
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY
WIKIPEDIA
PENTOXIFYLLINE
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY
ECHA (EC/EINECS)
229-374-5
Created by admin on Fri Dec 15 15:33:57 GMT 2023 , Edited by admin on Fri Dec 15 15:33:57 GMT 2023
PRIMARY
SMS_ID
100000091628
Created by admin on Fri Dec 15 15:33:58 GMT 2023 , Edited by admin on Fri Dec 15 15:33:58 GMT 2023
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
URINE
DEGRADENT -> PARENT
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METABOLITE ACTIVE -> PARENT
MINOR
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METABOLITE ACTIVE -> PARENT
OCCURS DURING FIRST PASS METABOLISM. CONCENTRATION MAY 10x HIGHER THAN PENTOXIFYLLINE
MAJOR
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APPEARS TO OCCUR PREDOMINANTLY IN RED BLOOD CELLS THROUGH NADPH REDUCTASE ENZYMES
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Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION