化合物信息

Drug Groups

approved

Description

Diflunisal, a salicylate derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with pharmacologic actions similar to other prototypical NSAIAs. Diflunisal possesses anti-inflammatory, analgesic and antipyretic activity. Though its mechanism of action has not been clearly established, most of its actions appear to be associated with inhibition of prostaglandin synthesis via the arachidonic acid pathway. Diflunisal is used to relieve pain accompanied with inflammation and in the symptomatic treatment of rheumatoid arthritis and osteoarthritis.

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 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.

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

Biotransformation

Hepatic, primarily via glucuronide conjugation (90% of administered dose).

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.

Half Life

8 to 12 hours

Protein Binding

At least 98 to 99% of diflunisal in plasma is bound to proteins.

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.

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