Preclinical overview of nabumetone. Pharmacology, bioavailability, metabolism, and toxicology.
Nabumetone is a novel nonacidic nonsteroidal anti-inflammatory drug (NSAID) developed by Beecham Pharmaceuticals. After absorption, nabumetone undergoes extensive metabolism, the main circulating material being 6-methoxy-2-naphthylacetic acid, (BRL 10720). This, unlike nabumetone, is a potent inhibitor of prostaglandin synthesis and is considered to be the active anti-inflammatory metabolite. Nabumetone is active in all standard laboratory models of inflammation and has a greater ratio of active to gastric irritant doses (therapeutic ratio) in the rat than any other NSAID tested. The lack of effect on the gastric mucosa in all species has been a notable feature of the toxicology studies. In humans, relative bioavailability is similar after administration of different dose levels, the mean terminal plasma half-life of BRL 10720 being about 24 hours, allowing for once-daily dosing. The half-life of BRL 10720 does not change on repeated dosing, and no unexpected or irreversible accumulation occurs in elderly patients.
Beecham Pharmaceuticals, Medicinal Research Center, Harlow, Essex, United Kingdom.
F R
FR
Mangan
J D
JD
Flack
D
D
Jackson
D000367:Age Factors; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D001168:Arthritis / Q000378:metabolism; D001682:Biological Availability; D001711:Biotransformation; D002074:Butanones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D000077430:Nabumetone; D013270:Stomach / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D000077430:Nabumetone