| Indication |
For acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis. |
| Pharmacodynamics |
Nabumetone is a naphthylalkanone. Is is a non-selective
prostaglandin G/H synthase (a.k.a. cyclooxygenase or COX) inhibitor that
acts on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2).
Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid
to prostaglandin G2 and prostaglandin G2 to prostaglandin H2.
Prostaglandin H2 is the precursor to a number of prostaglandins involved
in fever, pain, swelling, inflammation, and platelet aggregation. The
parent compound is a prodrug that undergoes hepatic biotransformation to
the active compound, 6-methoxy-2-naphthylacetic acid (6MNA). The
analgesic, antipyretic and anti-inflammatory effects of NSAIDs occur as a
result of decreased prostaglandin synthesis. |
| Mechanism of action |
The parent compound is a prodrug, which undergoes hepatic
biotransformation to the active component, 6-methoxy-2-naphthylacetic
acid (6MNA), that is a potent inhibitor of prostaglandin synthesis, most
likely through binding to the COX-2 and COX-1 receptors. |
| Absorption |
Well absorbed from the gastrointestinal tract. Coadministration of
food increases the rate of absorption and subsequent appearance of 6MNA
(the active metabolite) in the plasma but does not affect the extent of
conversion of nabumetone into 6MNA. |
| Volume of distribution |
Not Available |
| Protein binding |
The active metabolite, 6MNA, is more than 99% bound to plasma proteins. |
| Metabolism |
Undergoes rapid biotransformation to the principal active
metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). Approximately 35% of
a 1000 mg oral dose of nabumetone is converted to 6MNA and 50% is
converted into unidentified metabolites which are subsequently excreted
in the urine. |
| Route of elimination |
Approximately 35% of a 1000 mg oral dose of nabumetone is
converted to 6MNA and 50% is converted into unidentified metabolites
which are subsequently excreted in the urine. |
| Half life |
Approximately 23 hours for the active metabolite, 6MNA. Increased in patients with renal insufficiency. |
| Clearance |
|
| Toxicity |
The one overdose occurred in a 17-year-old female patient who had a
history of abdominal pain and was hospitalized for increased abdominal
pain following ingestion of 30 nabumetone tablets (15 grams total).
Stools were negative for occult blood and there was no fall in serum
hemoglobin concentration. The patient had no other symptoms. |
