| Indication |
Flurbiprofen tablets are indicated for the acute or long-term
symptomatic treatment of rheumatoid arthritis, osteorarthritis and
anklosing spondylitis. It may also be used to treat pain associated with
dysmenorrhea and mild to moderate pain accompanied by inflammation
(e.g. bursitis, tendonitis, soft tissue trauma). Topical ophthalmic
formulations may be used pre-operatively to prevent intraoperative
miosis. |
| Pharmacodynamics |
Flurbiprofen, a nonsteroidal anti-inflammatory agent (NSAIA) of
the propionic acid class, is structually and pharmacologically related
to fenoprofen, ibuprofen, and ketoprofen, and has similar
pharmacological actions to other prototypica NSAIAs. Flurbiprofen
exhibits antiinflammatory, analgesic, and antipyretic activities. The
commercially available flurbiprofen is a racemic mixture of (+)S- and
(-) R-enantiomers. The S-enantiomer appears to possess most of the
anti-inflammatory, while both enantiomers may possess analgesic
activity. |
| Mechanism of action |
Similar to other NSAIAs, the anti-inflammatory effect of
flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX),
the enzyme responsible for the conversion of arachidonic acid to
prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the
prostaglandin synthesis pathway. This effectively decreases the
concentration of prostaglandins involved in inflammation, pain, swelling
and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits
the activity of both COX-1 and -2. It is also one of the most potent
NSAIAs in terms of prostaglandin inhibitory activity. |
| Absorption |
Fluribiprofen is rapidly and almost completely absorbed following
oral administration. Peak plasma concentrations are reached 0.5 - 4
hours after oral administration. |
| Volume of distribution |
- 14 L [Normal Healthy Adults]
- 12 L [Geriatric Arthritis Patients]
- 10 L [End Stage Renal Disease Patients]
- 14 L [Alcoholic Cirrhosis Patients]
- 0.12 L/kg
|
| Protein binding |
> 99% bound, primarily to albumin. Binds to a different primary
binding site on albumin than anticoagulants, sulfonamides and
phenytoin. |
| Metabolism |
Hepatic. Cytochrome P450 2C9 plays an important role in the
metabolism of flurbiprofen to its major metabolite,
4’-hydroxy-flurbiprofen. The 4’-hydroxy-flurbiprofen metabolite showed
little anti-inflammatory activity in animal models of inflammation. |
| Route of elimination |
Flurbiprofen is poorly excreted into human milk. Following dosing
with flurbiprofen, less than 3% of flurbiprofen is excreted unchanged in
the urine, with about 70% of the dose eliminated in the urine as parent
drug and metabolites. Renal elimination is a significant pathway of
elimination of flurbiprofen metabolites. |
| Half life |
R-flurbiprofen, 4.7 hours; S-flurbiprofen, 5.7 hours |
| Clearance |
Not Available |
| Toxicity |
LD50=10 mg/kg (orally in dogs).
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 flurbiprofen. Flurbiprofen may increase blood
pressure and/or cause fluid retention and edema. Use caution in patients
with fluid retention or heart failure. Risk of GI toxicity including
bleeding, ulceration and perforation. Risk of direct renal injury,
including renal papillary necrosis. Anaphylactoid and serious skin
reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic
epidermal necrolysis) may occur. Common adverse events include abdominal
pain, constipation, diarrhea, dyspepsia, flatulence, GI bleeding, GI
perforation, nausea, peptic ulcer, vomiting, renal function
abnormalities, anemia, dizziness, edema, liver function test
abnormalities, headache, prolonged bleeding time, pruritus, rash,
tinnitus. |
