Nabumetone

Molecular formula CisH eO Molecular weight 228.3 CAS Registry No. 42924-53-8 

Sample preparation 2 mL Plasma -i- 200 (aL 200 jjig/mL naproxen -I- 1 mL 500 mM pH 3 citrate buffer -I- 100 pL 1 M HCl -t- 5 mL ether, shake for 2 min, centrifuge. Remove the organic layer and evaporate it to dryness, reconstitute the residue in MeCN, inject an aliquot. 

Guard column Resolve CIS Guard-Pak (Waters) Column CIS Radial-Pak (Waters) 

Mobile phase MeCN sodium acetate buffer 60 40 Detector UV 2S0 

Aronoff, G.R. Population pharmacokinetics of the active metabolite of nabumetone in renal dysfunction. Clin.Pharmacol.Ther, 1995, 57, 622-627 

Sample preparation 0.5 mL Plasma -I- 2.5 xL 400 pg/mL 6-chloro-2-naphthylacetic acid in acetone, mix on a whirlmixer, add 6 mL n-hexane ethyl acetate 50 50, add 0.7 mL 1.5 M HCl, shake mechanically for 30 min, centrifuge at 1500 g for 10 min. mover organic layer and evaporate it to dryness at 37° under a stream of nitrogen. Dissolve residue in mobile phase, centrifuge, inject a 20 xL aliquot. 

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Metabolic pathways rarely lead to breaking a carbon-carbon bond however, there are exceptions such as the conversion of the prodrug nabumetone to an active nonsteroidal anti-inflammatory agent as shown in Figure 4.84 (153). Although the mechanism of this conversion is unknown, if oxidation leads to two adjacent carbonyl groups it weakens the carbon-carbon bond and further oxidation leads the rupture of this bond. 

Mangan FR, Flack JD, Jackson D. Preclinical overview of nabumetone. Pharmacology, bioavailability, metabolism, and toxicology. Am J Med 1987 83(4B) 6-10. 

These studies have been extended and confirmed with A-monosubsti-tuted and A, A-di substituted carbamoylmethyl esters of 6-methoxy-2-naph-thylacetic acid [38], This compound, a close analogue of naproxen (8.26), is the active metabolite of the anti-inflammatory agent nabumetone. The A-substituents investigated were mostly lower alkyl and oxygenated alkyl groups. The compounds were quite stable in buffer under physiological... 

Moricizine 50 Morphine 50 Morphine Sul te 50 Motrin 41 MS Contin 50 Mucomyst 12 Mupirocin 50 Myambutol 33 Mycelex 26 Mycifiadin 51 Myciguent 51 Mycobutin 60 Mycolog-ll 77 Mycostatin 53 Mylanta 47 Mysoline 57 Nabumetone 50 Nadolol 50 Nafarelin 50 Nafdl 50 Nafcillin 50 Naftifine 50 Naftin 50... 

NABUMETONE Recommended starting dose is 1,000 mg as a single dose with or without food. Some patients may obtain more symptomatic relief from 1,500 to 2,000 mg/day. Nabumetone can be given either once or twice/day. Dosages greater than 2,000 mg/day have not been studied. 

Category C (etodolac, ketorolac, mefenamic acid, meloxicam, nabumetone, oxaprozin, tolmetin, piroxicam, celecoxib). All NSAIDs are Category D if used in the third trimester or near delivery. Avoid during pregnancy, especially in the third trimester. 

CNS Dizziness (mefenamic acid, meloxicam, piroxicam, flurbiprofen, diciofenac, fenoprofen) headache (ketorolac, fenoprofen, indomethacin, diclofenac, flurbiprofen, meclofenamate, meloxicam, nabumetone, naproxen, tolmetin, ketoprofen, sulindac, celecoxib, mefenamic acid, piroxicam, ibuprofen) somnolence/drowsiness (fenoprofen, naproxen) asthenia (tolmetin, etodolac) malaise (etodolac) fatigue (indomethacin) insomnia (meloxicam). Dermatologic Rash/dermatitis, including maculopapular type (ibuprofen, sulindac, meclofenamate, oxaprozin, nabumetone, mefenamic acid, meloxicam) desquamation angioneurotic edema ecchymosis petechiae purpura alopecia pruritus (nabumetone, naproxen) eczema skin discoloration hyperpigmentation skin irritation peeling skin eruptions (naproxen). 

Nabumetone (Relafen) Naproxen (Aleve, Naprosyn, Anaprox) Oxaprozin (Daypro, Daypro ALTA) Piroxicam (Feldene) Sulindac (Clinoril) Tohnetin (Tolectin)... 

Nabumetone (Relafen) has antiinflammatory, antipyretic, and analgesic properties. It is converted by liver enzymes to an active metabolite that is a potent COX inhibitor. Although nabumetone shares many of the adverse effects of other NSAIDs, it appears to produce a lower incidence of GI ulceration. 

Take nabumetone with food if GI upset occurs... 

Nabumetone may cause serious GI bleeding with or without pain avoid aspirin during nabumetone therapy because it increases the risk of GI bleeding... 

Nabumetone may cause confusion or dizziness avoid performing tasks that require mental alertness or motor skills until response to the drug has been established... 

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