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Details

Stereochemistry ACHIRAL
Molecular Formula C13H8F2O3
Molecular Weight 250.1976
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIFLUNISAL

SMILES

OC(=O)C1=CC(=CC=C1O)C2=C(F)C=C(F)C=C2

InChI

InChIKey=HUPFGZXOMWLGNK-UHFFFAOYSA-N
InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)

HIDE SMILES / InChI

Description

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It was developed by Merck Sharp & Dohme in 1971 after showing promise in a research project studying more potent chemical analogs of aspirin. Diflunisal is an aspirin-like nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis.In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DOLOBID
Primary
DOLOBID
Primary
DOLOBID

Cmax

ValueDoseCo-administeredAnalytePopulation
173.66 mg/L
500 mg single, oral
DIFLUNISAL plasma
Homo sapiens
186 μg/mL
100 mg 1 times / day steady-state, oral
DIFLUNISAL plasma
Homo sapiens
150 μg/mL
500 mg 2 times / day steady-state, oral
DIFLUNISAL plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
678 μg × h/mL
500 mg single, oral
DIFLUNISAL plasma
Homo sapiens
2839 μg × h/mL
100 mg 1 times / day steady-state, oral
DIFLUNISAL plasma
Homo sapiens
2782 μg × h/mL
500 mg 2 times / day steady-state, oral
DIFLUNISAL plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
11.4 h
500 mg single, oral
DIFLUNISAL plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer









Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
For mild to moderate pain, an initial dose of 1000 mg followed by 500 mg every 12 hours is recommended for most patients. Following the initial dose, some patients may require 500 mg every 8 hours. A lower dosage may be appropriate depending on such factors as pain severity, patient response, weight, or advanced age; for example, 500 mg initially, followed by 250 mg every 8-12 hours. For osteoarthritis and rheumatoid arthritis, the suggested dosage range is 500 mg to 1000 mg daily in two divided doses. The dosage of DOLOBID may be increased or decreased according to patient response. Maintenance doses higher than 1500 mg a day are not recommended.
Route of Administration: Oral
In Vitro Use Guide
To a solution of human serum albumin (Sigma, 40 mg/mL in 50 mM phosphate buffered saline, pH 7.4), Diflunisal were added to a final concentration of 20 mkg/mL in 1 mL total volume. The mixtures were allowed to equilibrate for 1 h at room temperature and were then centrifuged at 86 000 x g for 18 h. The resulting gradient was fractionated into 5 x 200 mkL samples and extracted with acetonitrile in preparation for analysis by reverse-phase high-performance liquid chromatography. A mobile phase of 55:45 CH3CN/0.1% trifluoroacetic acid at a flow rate of 1 mL/min with a Luna C18 (100 x 4.6 mm) column and ultraviolet detection at 210 nm were used for compound detection. To calculate the fraction of free Diflunisal , the area of the chromatographic compound peak for the upper protein-free fraction was divided by the total peak area for the entire gradient.