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Details

Stereochemistry ACHIRAL
Molecular Formula C13H7F2O3.Na
Molecular Weight 272.1795
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIFLUNISAL SODIUM

SMILES

[Na+].OC1=CC=C(C=C1C([O-])=O)C2=CC=C(F)C=C2F

InChI

InChIKey=TWNIMRJXRIWUKA-UHFFFAOYSA-M
InChI=1S/C13H8F2O3.Na/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);/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula C13H7F2O3
Molecular Weight 249.1897
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula Na
Molecular Weight 22.98976928
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Curator's Comment: Studies in baboons to determine passage across the blood-brain barrier have shown that only small quantities of diflunisal, under normal or acidotic conditions are transported into the cerebrospinal fluid (CSF). The ratio of blood/CSF concentrations after intravenous doses of 50 mg/kg or oral doses of 100 mg/kg of diflunisal was 100:1. In contrast, oral doses of 500 mg/kg of aspirin resulted in a blood/CSF ratio of 5:1.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DOLOBID

Approved Use

Carefully consider the potential benefits and risks of diflunisal tablets and other treatment options before deciding to use diflunisal tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS). Diflunisal tablets are indicated for acute or long-term use for symptomatic treatment of the following: Mild to moderate pain Osteoarthritis Rheumatoid arthritis

Launch Date

1982
Primary
DOLOBID

Approved Use

Carefully consider the potential benefits and risks of diflunisal tablets and other treatment options before deciding to use diflunisal tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS). Diflunisal tablets are indicated for acute or long-term use for symptomatic treatment of the following: Mild to moderate pain Osteoarthritis Rheumatoid arthritis

Launch Date

1982
Primary
DOLOBID

Approved Use

Carefully consider the potential benefits and risks of diflunisal tablets and other treatment options before deciding to use diflunisal tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS). Diflunisal tablets are indicated for acute or long-term use for symptomatic treatment of the following: Mild to moderate pain Osteoarthritis Rheumatoid arthritis

Launch Date

1982
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
173.66 mg/L
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIFLUNISAL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
186 μg/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DIFLUNISAL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
150 μg/mL
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DIFLUNISAL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
678 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIFLUNISAL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2839 μg × h/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DIFLUNISAL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2782 μg × h/mL
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DIFLUNISAL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11.4 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIFLUNISAL plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1500 mg 1 times / day steady, oral
Highest studied dose
Dose: 1500 mg, 1 times / day
Route: oral
Route: steady
Dose: 1500 mg, 1 times / day
Sources:
healthy, 35 years
Health Status: healthy
Age Group: 35 years
Sex: M+F
Sources:
500 mg 1 times / day steady, oral
Dose: 500 mg, 1 times / day
Route: oral
Route: steady
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 60.7 years (range: 25 - 80 years)
Health Status: unhealthy
Age Group: 60.7 years (range: 25 - 80 years)
Sex: M+F
Sources:
Disc. AE: Impaired renal function, Thrombocytopenia...
AEs leading to
discontinuation/dose reduction:
Impaired renal function (2 patients)
Thrombocytopenia (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Thrombocytopenia 1 patient
Disc. AE
500 mg 1 times / day steady, oral
Dose: 500 mg, 1 times / day
Route: oral
Route: steady
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 60.7 years (range: 25 - 80 years)
Health Status: unhealthy
Age Group: 60.7 years (range: 25 - 80 years)
Sex: M+F
Sources:
Impaired renal function 2 patients
Disc. AE
500 mg 1 times / day steady, oral
Dose: 500 mg, 1 times / day
Route: oral
Route: steady
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 60.7 years (range: 25 - 80 years)
Health Status: unhealthy
Age Group: 60.7 years (range: 25 - 80 years)
Sex: M+F
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Chemometric assisted solid-phase microextraction for the determination of anti-inflammatory and antiepileptic drugs in river water by liquid chromatography-diode array detection.
2008-11-21
Chemical substructures that enrich for biological activity.
2008-11-01
In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II.
2008-10-15
Simultaneous determination of two anti-inflammatory drugs in serum using isopotential fluorimetry.
2008-09-05
Differential scanning calorimetry study on drug release from an inulin-based hydrogel and its interaction with a biomembrane model: pH and loading effect.
2008-09-02
Simultaneous determination of naproxen and diflunisal using synchronous luminescence spectrometry.
2008-09
100,000-fold concentration of anions in capillary zone electrophoresis using electroosmotic flow controlled counterflow isotachophoretic stacking under field amplified conditions.
2008-08-15
Species differences in inhibition potential of nonsteroidal anti-inflammatory drugs against estradiol 3beta-glucuronidation between rats, dogs, and humans.
2008-07
Thermodynamic studies of Fenbufen, Diflunisal, and Flurbiprofen: sublimation, solution and solvation of biphenyl substituted drugs.
2008-06-05
The modulation of transthyretin tetramer stability by cysteine 10 adducts and the drug diflunisal. Direct analysis by fluorescence-detected analytical ultracentrifugation.
2008-05-02
Molecular interactions in lipophilic environments studied by electrochemistry at interfaces between immiscible electrolyte solutions.
2008-01-01
Pre-emptive analgesia for removal of nasal packing: A double-blind placebo controlled study.
2007-12
FluSTAR, a novel influenza surveillance system: outcomes from the 2005-2006 flu season.
2007-09
In vivo stabilization of mutant human transthyretin in transgenic mice.
2007-09
Non-steroidal anti-inflammatory drug (NSAID)-derived poly(anhydride-esters) in bone and periodontal regeneration.
2007-07
Diflunisal salts of bupivacaine, lidocaine and morphine. Use of the common ion effect for prolonging the release of bupivacaine from mixed salt suspensions in an in vitro dialysis model.
2007-07
Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents.
2007-07
Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction?
2007-05
The effect of 2 Hz and 100 Hz electrical stimulation of acupoint on ankle sprain in rats.
2007-04
Comparison of inhibition potentials of drugs against zidovudine glucuronidation in rat hepatocytes and liver microsomes.
2007-04
Simultaneous determination of paracetamol, caffeine and propyphenazone in ternary mixtures by micellar electrokinetic capillary chromatography.
2007-03-01
Transdermal delivery of nonsteroidal anti-inflammatory drugs mediated by polyamidoamine (PAMAM) dendrimers.
2007-03
Inhibitory potential of nonsteroidal anti-inflammatory drugs on UDP-glucuronosyltransferase 2B7 in human liver microsomes.
2007-02
A comparison of pre-emptive analgesic efficacy of diflunisal and lornoxicam for postoperative pain management: a prospective, randomized, single-blind, crossover study.
2007-02
Direct determination of closely overlapping drug mixtures of diflunisal and salicylic acid in serum by means of derivative matrix isopotential synchronous fluorescence spectrometry.
2007-01-30
Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis.
2006-12
Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis.
2006-12
Prediction of plasma protein binding displacement and its implications for quantitative assessment of metabolic drug-drug interactions from in vitro data.
2006-12
Allosteric modulation of [3H]EBOB binding to GABAA receptors by diflunisal analogues.
2006-12
In-vitro study on the competitive binding of diflunisal and uraemic toxins to serum albumin and human plasma using a potentiometric ion-probe technique.
2006-11
Cell based screening of inhibitors of transthyretin aggregation.
2006-09-29
In vitro drug interaction between diflunisal and indomethacin via glucuronidation in humans.
2006-09
Drug Insight: emerging therapies for amyloidosis.
2006-05
pH-sensitive hydrogels based on bovine serum albumin for oral drug delivery.
2006-04-07
Thermally responsive polymeric micelles self-assembled by amphiphilic polyphosphazene with poly(N-isopropylacrylamide) and ethyl glycinate as side groups: polymer synthesis, characterization, and in vitro drug release study.
2006-03-15
Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide.
2006-03
Predicting the pharmacokinetics of acyl glucuronides and their parent compounds in disease states.
2006-02
Pharmaceutical quality control of acid and neutral drugs based on competitive self-assembly in amphiphilic systems.
2006-01
In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant human UDP-glucuronosyltransferase 1A9--potent inhibition by niflumic acid.
2006-01
Determination of nonsteroidal antiinflammatory drugs in water samples using liquid chromatography coupled with diode-array detector and mass spectrometry.
2005-11
Dendrimers as potential drug carriers. Part I. Solubilization of non-steroidal anti-inflammatory drugs in the presence of polyamidoamine dendrimers.
2005-11
Bupivacaine salts of diflunisal and other aromatic hydroxycarboxylic acids: aqueous solubility and release characteristics from solutions and suspensions using a rotating dialysis cell model.
2005-11
Role of monocarboxylic acid transporters in the cellular uptake of NSAIDs.
2005-09
Radical cross-linked albumin microspheres as potential drug delivery systems: preparation and in vitro studies.
2005-07-23
Human transthyretin in complex with iododiflunisal: structural features associated with a potent amyloid inhibitor.
2005-06-01
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005-06
Solid-state fluorescence studies of some polymorphs of diflunisal*.
2005-06
Design, synthesis, and biological evaluation of N-acetyl-2-carboxybenzenesulfonamides: a novel class of cyclooxygenase-2 (COX-2) inhibitors.
2005-04-01
UDP-glucuronosyltransferases and clinical drug-drug interactions.
2005-04
Photosensitizing effect of some nonsteroidal antiinflammatory drugs on natural and artificial membranes: dependence on phospholipid composition.
2005-02
Patents

Sample Use Guides

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
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.
Substance Class Chemical
Created
by admin
on Mon Mar 31 21:56:02 GMT 2025
Edited
by admin
on Mon Mar 31 21:56:02 GMT 2025
Record UNII
MJG4K58KPV
Record Status Validated (UNII)
Record Version
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Name Type Language
(1,1'-BIPHENYL)-3-CARBOXYLIC ACID, 2',4'-DIFLUORO-4-HYDROXY-, MONOSODIUM SALT
Preferred Name English
DIFLUNISAL SODIUM
Common Name English
SODIUM DIFLUNISAL
Systematic Name English
(1,1'-BIPHENYL)-3-CARBOXYLIC ACID, 2',4'-DIFLUORO-4-HYDROXY-, SODIUM SALT (1:1)
Systematic Name English
Code System Code Type Description
FDA UNII
MJG4K58KPV
Created by admin on Mon Mar 31 21:56:02 GMT 2025 , Edited by admin on Mon Mar 31 21:56:02 GMT 2025
PRIMARY
PUBCHEM
23677945
Created by admin on Mon Mar 31 21:56:02 GMT 2025 , Edited by admin on Mon Mar 31 21:56:02 GMT 2025
PRIMARY
EPA CompTox
DTXSID00233033
Created by admin on Mon Mar 31 21:56:02 GMT 2025 , Edited by admin on Mon Mar 31 21:56:02 GMT 2025
PRIMARY
ECHA (EC/EINECS)
282-223-5
Created by admin on Mon Mar 31 21:56:02 GMT 2025 , Edited by admin on Mon Mar 31 21:56:02 GMT 2025
PRIMARY
CAS
84145-00-6
Created by admin on Mon Mar 31 21:56:02 GMT 2025 , Edited by admin on Mon Mar 31 21:56:02 GMT 2025
PRIMARY
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ACTIVE MOIETY