Nabumetone is a nonsteroidal anti-inflammatory
prodrug, which exerts its pharmacological effects via the metabolite
6-methoxy-2-naphthylacetic acid (6-MNA).
Nabumetone itself is non-acidic and, following absorption, it undergoes extensive first-pass metabolism to form the main circulating active metabolite (6-MNA) which is a much more potent inhibitor of preferentially
cyclo-oxygenase (COX)-2. The three major metabolic pathways of
nabumetone are O-demethylation, reduction of the
ketone to an alcohol, and an oxidative cleavage of the side-chain occurs to yield
acetic acid derivatives. Essentially no unchanged
nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the urine from which 80% of the dose can be recovered and another 10% in faeces.
Nabumetone is clinically used mainly for the management of patients with
osteoarthritis (OA) or
rheumatoid arthritis (RA) to reduce
pain and
inflammation. The clinical efficacy of
nabumetone has also been evaluated in patients with
ankylosing spondylitis,
soft tissue injuries and juvenile RA. The optimum oral dosage of
nabumetone for OA patients is 1 g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients,
nabumetone 1 g at bedtime is optimal, but an additional 0.5-1 g can be administered in the morning for patients with persistent symptoms. In RA,
nabumetone has shown a comparable clinical efficacy to
aspirin (
acetylsalicylic acid),
diclofenac,
piroxicam,
ibuprofen and
naproxen. Clinical trials and a decade of worldwide safety data and long-term postmarketing surveillance studies show that
nabumetone is generally well tolerated. The most frequent adverse effects are those commonly seen with COX inhibitors, which include diarrhoea,
dyspepsia,
headache,
abdominal pain and
nausea. In common with other COX inhibitors,
nabumetone may increase the risk of GI perforations, ulcerations and bleedings (PUBs). However, several studies show a low incidence of PUBs, and on a par with the numbers reported from studies with COX-2 selective inhibitors and considerably lower than for nonselective COX inhibitors. This has been attributed mainly to the non-acidic chemical properties of
nabumetone but also to its COX-1/
COX-2 inhibitor profile. Through its metabolite 6-MNA,
nabumetone has a dose-related effect on platelet aggregation, but no effect on bleeding time in clinical studies. Furthermore, several short-term studies have shown little to no effect on renal function. Compared with COX-2 selective inhibitors,
nabumetone exhibits similar anti-inflammatory and
analgesic properties in patients with
arthritis and there is no evidence of excess GI or other forms of complications to date.