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
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
| 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 | 22.9898 |
| 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
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL230 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | DOLOBID Approved UseCarefully 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 Date3.88022403E11 |
|||
| Primary | DOLOBID Approved UseCarefully 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 Date3.88022403E11 |
|||
| Primary | DOLOBID Approved UseCarefully 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 Date3.88022403E11 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
150 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3841206 |
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 |
|
186 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3841206 |
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 |
|
173.66 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2029803/ |
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2782 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3841206 |
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 |
|
2839 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3841206 |
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 |
|
678 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2029803/ |
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 |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
11.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2029803/ |
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
| Dose | Population | Adverse 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 Co-administed with:: indometacin(100 mg single-dose rectally) Sources: |
healthy, 35 years n = 8 Health Status: healthy Age Group: 35 years Sex: M+F Population Size: 8 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) n = 40 Health Status: unhealthy Condition: Hereditary ATTR amyloidosis Age Group: 60.7 years (range: 25 - 80 years) Sex: M+F Population Size: 40 Sources: |
Disc. AE: Impaired renal function, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Impaired renal function (2 patients) Sources: Thrombocytopenia (1 patient) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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) n = 40 Health Status: unhealthy Condition: Hereditary ATTR amyloidosis Age Group: 60.7 years (range: 25 - 80 years) Sex: M+F Population Size: 40 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) n = 40 Health Status: unhealthy Condition: Hereditary ATTR amyloidosis Age Group: 60.7 years (range: 25 - 80 years) Sex: M+F Population Size: 40 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| yes [IC50 19.4 uM] | ||||
| yes [IC50 33 uM] | ||||
| yes [IC50 51 uM] | ||||
| yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| yes | ||||
| yes | ||||
| yes |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Position Paper on urine alkalinization. | 2004 |
|
| Utilization of animal studies to determine the effects and human risks of environmental toxicants (drugs, chemicals, and physical agents). | 2004 Apr |
|
| Drug delivery devices based on mesoporous silicate. | 2004 Jan-Feb |
|
| Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative. | 2004 Jul 15 |
|
| Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. | 2004 Jul 2 |
|
| Inverse gene expression patterns for macrophage activating hepatotoxicants and peroxisome proliferators in rat liver. | 2004 Jun 1 |
|
| Compounds exhibiting selective efficacy for different beta subunits of human recombinant gamma-aminobutyric acid A receptors. | 2004 Nov |
|
| Aqueous-phase, palladium-catalyzed cross-coupling of aryl bromides under mild conditions, using water-soluble, sterically demanding alkylphosphines. | 2004 Nov 12 |
|
| UDP-glucuronosyltransferases and clinical drug-drug interactions. | 2005 Apr |
|
| Design, synthesis, and biological evaluation of N-acetyl-2-carboxybenzenesulfonamides: a novel class of cyclooxygenase-2 (COX-2) inhibitors. | 2005 Apr 1 |
|
| Photosensitizing effect of some nonsteroidal antiinflammatory drugs on natural and artificial membranes: dependence on phospholipid composition. | 2005 Feb |
|
| In vitro inhibitory effects of non-steroidal antiinflammatory drugs on UDP-glucuronosyltransferase 1A1-catalysed estradiol 3beta-glucuronidation in human liver microsomes. | 2005 Jan |
|
| Radical cross-linked albumin microspheres as potential drug delivery systems: preparation and in vitro studies. | 2005 Jul-Aug |
|
| Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
| Solid-state fluorescence studies of some polymorphs of diflunisal*. | 2005 Jun |
|
| Human transthyretin in complex with iododiflunisal: structural features associated with a potent amyloid inhibitor. | 2005 Jun 1 |
|
| Determination of nonsteroidal antiinflammatory drugs in water samples using liquid chromatography coupled with diode-array detector and mass spectrometry. | 2005 Nov |
|
| Role of monocarboxylic acid transporters in the cellular uptake of NSAIDs. | 2005 Sep |
|
| pH-sensitive hydrogels based on bovine serum albumin for oral drug delivery. | 2006 Apr 7 |
|
| Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis. | 2006 Dec |
|
| Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis. | 2006 Dec |
|
| Prediction of plasma protein binding displacement and its implications for quantitative assessment of metabolic drug-drug interactions from in vitro data. | 2006 Dec |
|
| Allosteric modulation of [3H]EBOB binding to GABAA receptors by diflunisal analogues. | 2006 Dec |
|
| Predicting the pharmacokinetics of acyl glucuronides and their parent compounds in disease states. | 2006 Feb |
|
| Pharmaceutical quality control of acid and neutral drugs based on competitive self-assembly in amphiphilic systems. | 2006 Jan |
|
| 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 Jan |
|
| Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide. | 2006 Mar |
|
| 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 Mar 15 |
|
| Drug Insight: emerging therapies for amyloidosis. | 2006 May |
|
| 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 Nov |
|
| In vitro drug interaction between diflunisal and indomethacin via glucuronidation in humans. | 2006 Sep |
|
| Cell based screening of inhibitors of transthyretin aggregation. | 2006 Sep 29 |
|
| The effect of 2 Hz and 100 Hz electrical stimulation of acupoint on ankle sprain in rats. | 2007 Apr |
|
| Inhibitory potential of nonsteroidal anti-inflammatory drugs on UDP-glucuronosyltransferase 2B7 in human liver microsomes. | 2007 Feb |
|
| A comparison of pre-emptive analgesic efficacy of diflunisal and lornoxicam for postoperative pain management: a prospective, randomized, single-blind, crossover study. | 2007 Feb |
|
| Direct determination of closely overlapping drug mixtures of diflunisal and salicylic acid in serum by means of derivative matrix isopotential synchronous fluorescence spectrometry. | 2007 Jan 30 |
|
| Non-steroidal anti-inflammatory drug (NSAID)-derived poly(anhydride-esters) in bone and periodontal regeneration. | 2007 Jul |
|
| 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 Jul |
|
| Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents. | 2007 Jul |
|
| Transdermal delivery of nonsteroidal anti-inflammatory drugs mediated by polyamidoamine (PAMAM) dendrimers. | 2007 Mar |
|
| Simultaneous determination of paracetamol, caffeine and propyphenazone in ternary mixtures by micellar electrokinetic capillary chromatography. | 2007 Mar 1 |
|
| Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? | 2007 May |
|
| 100,000-fold concentration of anions in capillary zone electrophoresis using electroosmotic flow controlled counterflow isotachophoretic stacking under field amplified conditions. | 2008 Aug 15 |
|
| Thermodynamic studies of Fenbufen, Diflunisal, and Flurbiprofen: sublimation, solution and solvation of biphenyl substituted drugs. | 2008 Jun 5 |
|
| Chemical substructures that enrich for biological activity. | 2008 Nov 1 |
|
| Chemometric assisted solid-phase microextraction for the determination of anti-inflammatory and antiepileptic drugs in river water by liquid chromatography-diode array detection. | 2008 Nov 21 |
|
| In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. | 2008 Oct 15 |
|
| Differential scanning calorimetry study on drug release from an inulin-based hydrogel and its interaction with a biomembrane model: pH and loading effect. | 2008 Sep 2 |
|
| Simultaneous determination of two anti-inflammatory drugs in serum using isopotential fluorimetry. | 2008 Sep 5 |
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
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Edited
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| Record UNII |
MJG4K58KPV
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| Record Status |
Validated (UNII)
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| Record Version |
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