Blood and Tissue Fluid Levels of a New Non-Steroidal Anti-Inflammatory Preparation of Nabumetone

Torre, D; Sampietro, Carmen; Maggiolo, Franco

doi:10.1177/030006058701500606

Cited by 4 publications

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“…The concentrations of 6MNA and nabumetone tested, 50 and 150 μ M , were in the range of 6MNA concentrations reported in the synovial fluid and serum, respectively ( Miehlke et al ., 1990 ), and also in the range of reported IC 50 's for 6MNA for COX‐1 (∼40 μ M ) and COX‐2 (∼150 μ M ) ( Davies, 1997 ; Warner et al ., 1999 ). Pharmacokinetic studies indicate that nabumetone is hepatically converted to 6MNA and that concentrations of nabumetone in the bloodstream are very low ( Haddock et al ., 1984 ; Torre et al ., 1987 ; Blower, 1992 ; Hyneck, 1992 ; Davies, 1997 ). However, only one study has addressed nabumetone concentrations in the joint.…”

Section: Discussionmentioning

confidence: 99%

“…Nabumetone is a nonsteroidal anti‐inflammatory drug (NSAID) used to treat osteoarthritis and RA ( Helfgott, 1994 ). In contrast to most other NSAIDs, nabumetone is a prodrug that undergoes hepatic conversion to 6‐methoxy‐2‐naphthylacetic acid (6MNA) ( Haddock et al ., 1984 ; Torre et al ., 1987 ), an active inhibitor of COX with some selectivity for COX‐2 ( Davies, 1997 ). Based on a limited number of pharmacokinetic studies, it has been assumed that nabumetone itself is either irrelevant or biologically inert.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of metalloproteinases and NF‐κB activation in rabbit synovial fibroblasts via E prostaglandins and Erk: contrasting effects of nabumetone and 6MNA

Pillinger

Dinsell

Apsel

et al. 2004

British J Pharmacology

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1 Nabumetone is a prodrug that is converted in vivo into 6-methoxy-2-naphthylacetic acid (6MNA), a cyclooxygenase inhibitor with anti-inflammatory properties. We tested the effects of nabumetone and 6MNA on the inflammatory responses of synovial fibroblasts (SFs). 2 Brief exposures to 6MNA (50-150 mM) had no effect on IL-1b/TNF-a (each 20 ng ml À1 )-stimulated Erk activation. Longer exposures depleted prostaglandin E 1 (PGE 1 ) as much as 70%, and stimulated Erk as much as 300%. Nabumetone (150 mM) inhibited Erk activation by 60-80%. 3 6MNA (50-150 mM) stimulated (E200%) and nabumetone (150 mM) inhibited (E50%) matrix metalloproteinase (MMP)-1, but not MMP-13 secretion from SFs. 6MNA stimulation of MMP-1 secretion was inhibited E30% by PGE 1 (1 mM) and E80% by the Erk pathway inhibitor UO126 (10 mM), confirming that PGE depletion and Erk activation mediate MMP-1 secretion by 6MNA. 4 Consistent with its role as an Erk inhibitor, nabumetone (150 mM) abrogated 6MNA enhancement of MMP-1 secretion. 5 UO126 (10 mM) and nabumetone (150 mM) inhibited (E70 and 40%, respectively), but 6MNA (150 mM) enhanced (E40%), NF-kB activation. 6 Our data indicate that 6MNA shares with other COX inhibitors several proinflammatory effects on synovial fibroblasts. In contrast, nabumetone demonstrates anti-inflammatory and potentially arthroprotective effects that have not been previously appreciated.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of metalloproteinases and NF‐κB activation in rabbit synovial fibroblasts via E prostaglandins and Erk: contrasting effects of nabumetone and 6MNA

Pillinger

Dinsell

Apsel

et al. 2004

British J Pharmacology

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Clinical Pharmacokinetics of Nabumetone

Davies

1997

Clinical Pharmacokinetics

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Nabumetone

Friedel¹,

Langtry²,

Buckley³

1993

Drugs

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Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) used to treat rheumatic and inflammatory conditions. It is absorbed as a nonacidic prodrug and is rapidly converted in the liver to an active metabolite which is responsible for its anti-inflammatory and analgesic effects. Published data from earlier comparative studies indicate that nabumetone, administered in a single dose of 1 to 2g daily, is as effective as aspirin, diclofenac, ibuprofen, indomethacin, naproxen and sulindac for the symptomatic treatment of rheumatoid arthritis, osteoarthritis, various nonarticular rheumatic conditions and acute soft tissue injury. Adverse events with nabumetone occur less frequently than with aspirin, and the incidence of gastrointestinal adverse events with nabumetone compares favourably with that of other NSAIDs. Rates of gastrointestinal ulceration and bleeding with nabumetone are low, apparently less than 1% annually. More recently, data from large-scale clinical trials and postmarketing surveillance studies have further confirmed the efficacy and tolerability of nabumetone. Thus, the drug should now be considered a well established member of this group of agents for the treatment of painful rheumatic and inflammatory conditions.

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Blood and Tissue Fluid Levels of a New Non-Steroidal Anti-Inflammatory Preparation of Nabumetone

Cited by 4 publications

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Regulation of metalloproteinases and NF‐κB activation in rabbit synovial fibroblasts via E prostaglandins and Erk: contrasting effects of nabumetone and 6MNA

Regulation of metalloproteinases and NF‐κB activation in rabbit synovial fibroblasts via E prostaglandins and Erk: contrasting effects of nabumetone and 6MNA

Clinical Pharmacokinetics of Nabumetone

Nabumetone

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