China
Africa
Explore chapters and articles related to this topic
Drugs Affecting the Musculoskeletal System
Published in Radhwan Nidal Al-Zidan, Drugs in Pregnancy, 2020
Risk Summary: It is better to be avoided during the 1st and 3rd Trimesters because the pregnancy experience in humans suggests a risk of pulmonary hypertension of the newborn, SABs, and congenital malformations linked to the use of Nabumetone.
N
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
The SPC recommends a dose reduction if CRCL<30 mL/min; however, an article by Brier et al. concluded that dosage adjustments may not be necessary with decreased renal function. The authors found an increase in the elimination half-life of 6-MNA, but stated that the increased half-life in patients with renal failure is offset by changes in the apparent volume of distribution that prevent the accumulation of 6-MNA. (Brier ME, Sloan RS, Aronoff GR. Population pharmacokinetics of the active metabolite of nabumetone in renal dysfunction. Clin Pharmacol Ther. 1995; 57(6): 622–7.)
Clinical pharmacology and therapeutics: nonopioids
Published in Nigel Sykes, Michael I Bennett, Chun-Su Yuan, Clinical Pain Management, 2008
Nabumetone is missing from these drug comparisons, yet has an impressive safety profile. Given over 12 weeks, it produced fewer endoscopic ulcers than ibuprofen, and no more than ibuprofen plus misoprostol 200 μg q.d.s.183[II] It was significantly less ulcerogenic than naproxen over five years and better tolerated.184[II] In a meta-analysis of 13 studies with 49,500 patients, it produced 10–36 times fewer GI adverse events than comparator NSAIDs.185[I] A six-week RCT revealed more patients satisfied with the analgesia from 12.5 mg of rofecoxib a day than 1 g of nabumetone daily, but the rofecoxib group suffered more overall and serious gastrointestinal adverse effects.186[II] A population-based cohort study indicated that Arthrotec (diclofenac plus misoprostol) produced marginally fewer hospitalizations for GI problems, although the lower confidence interval was 1.0; there was no difference in admissions for GI bleeding.187[III] However, nabumetone was safer than naproxen or diclofenac plus misoprostol given separately (presumably the misoprostol was often not taken). An extensive review of nabumetone is available.161
A metabolic pathway for the prodrug nabumetone to the pharmacologically active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA) by non-cytochrome P450 enzymes
Published in Xenobiotica, 2020
Kaori Matsumoto, Tetsuya Hasegawa, Kosuke Ohara, Chihiro Takei, Tomoyo Kamei, Junichi Koyanagi, Tamiko Takahashi, Masayuki Akimoto
Nabumetone (4-(6-methoxynaphthalen-2-yl)butan-2-one) is widely used as a non-acidic, non-steroidal anti-inflammatory prodrug. Pharmacokinetic studies have shown that nabumetone is subject to extensive hepatic biotransformation, resulting in several metabolites that are excreted into urine and feces and negligible amounts of the unchanged drug in plasma. After its oral administration, nabumetone undergoes hepatic oxidative cleavage of the aliphatic side chain to yield the physiologically active metabolite 6-methoxy-2-naphthylacetic acid (6-MNA), a potent cyclooxygenase-2 (COX-2) inhibitor. Two other metabolic pathways have been reported: O-demethylation and the reduction of the ketone to an alcohol (Haddock et al., 1984). 6-MNA undergoes further metabolism by cytochrome P450 2C9 (CYP2C9) to the inactive metabolite 6-hydroxy-2-naphthylacetic acid (6-HNA) (Matsumoto et al., 2011). Approximately 75% of the radiolabeled dose of nabumetone was recovered within 48 h in urine, and mainly consisted of 6-MNA and 6-HNA in their free and conjugated forms (Haddock et al., 1984).
Successes, failures, and future prospects of prodrugs and their clinical impact
Published in Expert Opinion on Drug Discovery, 2019
Parecoxib and nabumetone are both non-steroidal anti-inflammatory (NSAID) prodrugs. Parecoxib is a sulphonamide prodrug hydrolysed by hepatic carboxylesterase to valdecoxib. Parecoxib is an injectable cyclooxygenase-2 (COX- 2) inhibitor used for short term management of post-operative pain in the EU [67]. However, it was rejected by the FDA due to lack safety data [68]. Nabumetone is an aryl-alkanoic prodrug similar in structure to diclofenac. It undergoes hepatic biotransformation to 6-methoxy-2-napthylacetic acid. The active metabolite is a non-selective inhibitor of both COX-1 and COX-2. Nabumetone is prescribed for the management of pain associated with osteoarthritis and rheumatoid arthritis [69]. Similarly, sulindac is another prodrug belonging to aryl-alkanoic NSAIDs. Sulindac contains a sulfoxide moiety which requires in vivo reduction to sulphide. Little is known about the enzymes involved in this reduction, however, the drug is a substrate for methionine sulfoxide reductase [70].
Gut microbiota metabolizes nabumetone in vitro: Consequences for its bioavailability in vivo in the rodents with altered gut microbiome
Published in Xenobiotica, 2019
Lenka Jourova, Pavel Anzenbacher, Zuzana Matuskova, Rostislav Vecera, Jan Strojil, Milan Kolar, Milan Nobilis, Petra Hermanova, Tomas Hudcovic, Hana Kozakova, Miloslav Kverka, Eva Anzenbacherova
Nabumetone (4-(6-methoxy-2-naphthyl)-2-butanone) is widely used as a non-acidic, non-steroidal anti-inflammatory prodrug. After oral administration, nabumetone is converted by oxidative cleavage of its side chain to active metabolite 6-methoxy-2-naphthylacetic acid (6-MNA), a potent strong COX-2 inhibitor (Nobilis et al., 2013). Nabumetone is used mainly for the management of pain and inflammation in patients with osteoarthritis or rheumatoid arthritis (Hedner et al., 2004).