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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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PENTOXIL

Cmax

ValueDoseCo-administeredAnalytePopulation
1607 μg/mL
400 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens
272 ng/mL
100 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens
683 ng/mL
200 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens
719 ng/mL
600 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1228 ng × h/mL
400 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens
193 ng × h/mL
100 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens
380 ng × h/mL
200 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens
4842 ng × h/mL
600 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
0.84 h
400 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens
0.48 h
100 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens
0.39 h
200 mg single, oral
PENTOXIFYLLINE plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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
Record UNII
SD6QCT3TSU
Record Status Validated (UNII)
Record Version