QuickView for diflunisal (compound)

Summary
General Info

PubChem

PubChem Compound 3059

Name:	Diflunisal
PubChem Compound ID:	3059
Description:	A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of ASPIRIN.
Molecular formula:	C₁₃H₈F₂O₃
Molecular weight:	250.198 g/mol
Synonyms:	Diflunisal; [1,1'-Biphenyl]-3-carboxylic acid, 2',4'-difluoro-4-hydroxy-; KBio2_001442; Spectrum2_001012; MK-647; Spectrum4_000513; KBio2_006578; KBioGR_001085; KBioSS_001442; CAS-22494-42-4. show more » Diflunisal; [1,1'-Biphenyl]-3-carboxylic acid, 2',4'-difluoro-4-hydroxy-; KBio2_001442; Spectrum2_001012; MK-647; Spectrum4_000513; KBio2_006578; KBioGR_001085; KBioSS_001442; CAS-22494-42-4; 2',4'-difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid; 5-(2,4-difluorophenyl)salicylic acid; 3-BIPHENYLCARBOXYLIC ACID, 2',4'-DIFLUORO-4-HYDROXY-; MK 647; CHEBI:4538; 22494-42-4; 2',4'-Difluoro-4-hydroxy-(1,1'-biphenyl)-3-carboxylic acid; BRN 2654431; NINDS_000938; Prestwick_168; Spectrum_000962; 2',4'-difluoro-4-hydroxy-3-biphenylcarboxylic acid; Spectrum3_000392; 1FL; Prestwick1_000039; KBio1_000938; (1,1'-Biphenyl)-3-carboxylic acid, 2',4'-difluoro-4-hydroxy-; Diflunisal (JAN/USP); Diflunisal [USAN:BAN:INN:JAN]; D00130; KBio3_001423; NCGC00016765-01; Diflunisalum [INN-Latin]; Fluniget; 5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID; KBio2_004010; C01691; DivK1c_000938; Flovacil; MLS000028678; Dolobid (TN); Dolobis; EINECS 245-034-9; 2-(hydroxy)-5-(2,4-difluorophenyl)benzoic acid; SMR000058723; SPBio_001163; Dolobid; Prestwick0_000039; SPBio_002058 show less «

DrugBank

Identification

Name:	Diflunisal
Name (isomeric):	DB00861
Drug Type:	small molecule
Description:	A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of ASPIRIN.
Brand:	Fluodonil, Flovacil, Difludol, Dolisal, Dolobis, Dolobid, Flustar, Adomal, Fluniget, Dolobil
Category:	Analgesics, Non-Narcotic, Antipyretics, Cyclooxygenase Inhibitors, Analgesics, Anti-inflammatory Agents, Nonsteroidal Anti-inflammatory Agents (NSAIAs)
CAS number:	22494-42-4

Pharmacology

Indication:	For symptomatic treatment of mild to moderate pain accompanied by inflammation (e.g. musculoskeletal trauma, post-dental extraction, post-episiotomy), osteoarthritis, and rheumatoid arthritis.
Pharmacology:	Diflunisal is a nonsteroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance and addiction have not been reported. Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two r... show more » Diflunisal is a nonsteroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance and addiction have not been reported. Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1. The second difference is the removal of the 0-acetyl group from the carbon 4 position. Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure. show less «
Mechanism of Action:	The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor. 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 mod... show more » The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor. 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. show less «
Absorption:	Rapidly and completely absorbed following oral administration, with a bioavailability of 80-90%. Peak plasma concentrations are achieved 2 - 3 hours following oral administration.
Protein binding:	At least 98 to 99% of diflunisal in plasma is bound to proteins.
Biotransformation:	Hepatic, primarily via glucuronide conjugation (90% of administered dose).
Route of elimination:	The drug is excreted in the urine as two soluble glucuronide conjugates accounting for about 90% of the administered dose. Little or no diflunisal is excreted in the feces.
Half Life:	8 to 12 hours
Toxicity:	Oral LD₅₀ in rat, mouse, and rabbit is 392 mg/kg, 439 mg/kg, and 603 mg/kg, respectively. Symptoms of overdose include drowsiness, nausea, vomiting, diarrhea, hyperventilation, tachycardia, sweating, tinnitus, disorientation, stupor, and coma. The lowest dose without the presence of other medicines which caused death was 15 grams. Selective COX-2 inhibitors have been associated with increased risk of serious cardiovascular events (e.g. myocardial infarction, stroke) in some patients. Current data is insufficient to assess the cardiovascular risk of diflunisal. Short-term use does not appear to be associated with increased cardiovascular risk (except when used immediately following coronary artery bypass graft (CABG) surgery). Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Severe hepatic reactions, including cholestasis and/or jaundice, have been reported. May cause rash or hypersensitivity syndrome.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid alcohol.

Food slightly delays rate of absorption with no effect on extent of absorption.

Take with food to reduce gastric irritation.

Drug interaction:

Anisindione	The NSAID, diflunisal, may increase the anticoagulant effect of anisindione.
Dicumarol	The NSAID, diflunisal, may increase the anticoagulant effect of dicumarol.
Lithium	The NSAID, diflunisal, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Indomethacin	Concomitant therapy with the two NSAIDs, indomethacin and diflunisal, increases the risk of NSAID-related adverse effects (e.g. GI ulcers, bleeds, increased blood pressure).
Trandolapril	The NSAID, Diflunisal, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Diflunisal is initiated, discontinued or dose changed.

Anisindione	The NSAID, diflunisal, may increase the anticoagulant effect of anisindione.
Dicumarol	The NSAID, diflunisal, may increase the anticoagulant effect of dicumarol.
Lithium	The NSAID, diflunisal, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.
Indomethacin	Concomitant therapy with the two NSAIDs, indomethacin and diflunisal, increases the risk of NSAID-related adverse effects (e.g. GI ulcers, bleeds, increased blood pressure).
Trandolapril	The NSAID, Diflunisal, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Diflunisal is initiated, discontinued or dose changed.
Colesevelam	Bile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
Ginkgo biloba	Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Alendronate	Increased risk of gastric toxicity
Telmisartan	Concomitant use of Telmisartan and Diflunisal may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Acenocoumarol	The NSAID, diflunisal, may increase the anticoagulant effect of acenocoumarol.
Timolol	The NSAID, Diflunisal, may antagonize the antihypertensive effect of Timolol.
Treprostinil	The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Diflunisal. Monitor for increased bleeding during concomitant thearpy.
Methotrexate	The NSAID, diflunisal, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.
Warfarin	The antiplatelet effects of diflunisal may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
Probenecid	Probenecid increases toxicity of diflunisal

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Targets

Prostaglandin G/H synthase 2

Prostaglandin G/H synthase 1

Transporters

Solute carrier family 22 member 6

Carriers

Transthyretin

Serum albumin