[Properties and features of nabumetone].
Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) of the 2,6-disubstituted naphthylalkanone class. It is a prodrug metabolised to an active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), which preferentially inhibits cyclo-oxygenase-2 (COX-2) and has both anti-inflammatory and analgesic properties. The efficacy of nabumetone is comparable to that of other NSAIDs currently marketed in France for the treatment of rheumatoid arthritis and osteoarthritis. Nabumetone is metabolised to 6-MNA by extensive first-pass metabolism. This active metabolite is subsequently conjugated and excreted in urine. 6-MNA does not undergo enterohepatic recirculation, which may have implications for comparative gastrointestinal toxicity. Substantial concentrations of 6-MNA are achieved and maintained in synovial fluid, which is close to the proposed site of action in chronic arthropathies. The long plasma half-life of 6-MNA (20 to 24 hours) and its persistence in synovial fluid facilitate a once-daily dosage regimen. Nabumetone compares favourably with other NSAIDs with respect to its renal and gastrointestinal adverse effect profile, although increased clinical vigilance of drug-related adverse events relating to these organ systems is still recommended. In addition, in vitro experiments have shown this drug to have a good cartilage tolerability profile. Whether nabumetone has clinical utility in cardiovascular disorders remains to be determined. The unique pharmacokinetic and pharmacodynamic properties of nabumetone make it a welcome addition to the growing arsenal of drugs used in the treatment of chronic arthropathies. There may be clinical advantages in terms of the relative tolerability profile of nabumetone, given that this drug has a low COX-2/COX-1 ratio compared with other nonselective NSAIDs.
Davies
N M
NM
Faculté de Pharmacie, Université de Sydney, NSW, Australie. ndavies@pharm.usyd.edu.au
McLachlan
A J
AJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use*; D002074:Butanones / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D000077430:Nabumetone; D012216:Rheumatic Diseases / Q000188:drug therapy*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D000077430:Nabumetone