Antiinflammatory and gastrointestinal effects of nabumetone or its active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). Comparative studies with indomethacin.
6MNA, the active metabolite of the nonacidic antiinflammatory drug nabumetone, was investigated using intravenous administration for effects on (1) carrageenan paw edema and gastric irritancy compared with either oral nabumetone or both oral and intravenous indomethacin when given acutely and (2) gastrointestinal irritancy when given in repeat dosing studies. Oral doses of nabumetone or intravenous 6MNA produced effective antiinflammatory activity together with significant inhibition of paw exudate PGE2. Antiinflammatory oral doses of nabumetone or intravenous 6MNA produced minimal effects on gastric 6-keto PGF1 alpha production with an absence of gastric damage, in contrast with indomethacin. In repeat dose studies, 6MNA failed to induce gastrointestinal damage even at doses where general toxicity was evident. These results show that in the rat, 6MNA is an effective antiinflammatory drug but even in very high intravenous doses does not have the propensity to induce gastrointestinal damage.
Melarange
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SmithKline Beecham Pharmaceuticals, Research and Development Technologies, The Pinnacles, Harlow, Essex, UK.
Gentry
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C
O'Connell
C
C
Blower
P R
PR
Neil
C
C
Kelvin
A S
AS
Toseland
C D
CD
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002074:Butanones / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D004064:Digestive System / Q000187:drug effects* / Q000473:pathology; D004487:Edema / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D005528:Foot; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D007275:Injections, Intravenous; D008297:Male; D000077430:Nabumetone; D009280:Naphthaleneacetic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D009280:Naphthaleneacetic Acids; D011453:Prostaglandins; D002351:Carrageenan; C044612:6-methoxy-2-naphthylacetic acid; D000077430:Nabumetone; D007213:Indomethacin