Indications
Flurbiprofen is indicated for the acute or long-term symptomatic management of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Additionally, it is effective in alleviating pain associated with dysmenorrhea and provides relief for mild to moderate pain that is accompanied by inflammation, such as in conditions like bursitis, tendonitis, and soft tissue trauma. There are also topical ophthalmic formulations of flurbiprofen available, which can be used pre-operatively to prevent intraoperative miosis.
Pharmacodynamics
Flurbiprofen, belonging to the propionic acid class of nonsteroidal anti-inflammatory agents (NSAIDs), shares structural and pharmacological similarities with other prototypical NSAIDs such as fenoprofen, ibuprofen, and ketoprofen. It exhibits prominent anti-inflammatory, analgesic, and antipyretic properties. The flurbiprofen available commercially is a racemic mixture consisting of both the (+)S- and (-)R-enantiomers. The S-enantiomer predominantly contributes to the anti-inflammatory effects, while both enantiomers may possess analgesic properties.
Absorption
Following oral administration, flurbiprofen is rapidly and extensively absorbed into the bloodstream. Peak plasma concentrations are typically achieved within 0.5 to 4 hours post-administration, indicating efficient absorption dynamics of the compound.
Metabolism
The metabolism of flurbiprofen primarily occurs in the liver, with Cytochrome P450 2C9 playing a significant role in its biotransformation. This metabolic process results in the formation of the major metabolite, 4'-hydroxy-flurbiprofen. However, this metabolite exhibits minimal anti-inflammatory activity when evaluated in animal models of inflammation, underlining the parent compound's more critical role in therapeutic outcomes.
Mechanism of Action
Flurbiprofen functions as an anti-inflammatory agent by reversibly inhibiting cyclooxygenase (COX), the enzyme critical in the conversion of arachidonic acid to prostaglandin G2 (PGG2) and subsequently to prostaglandin H2 (PGH2) within the prostaglandin synthesis pathway. This inhibition results in a significant reduction of prostaglandins, which are key mediators of inflammation, pain, swelling, and fever. As a non-selective COX inhibitor, flurbiprofen targets both COX-1 and COX-2 enzymes. Notably, it is among the most potent non-steroidal anti-inflammatory agents (NSAIDs) regarding its ability to inhibit prostaglandin synthesis.
