Febuxostat D9

Febuxostat-d₉ is intended for use as an internal standard for the quantification of febuxostat by GC- or LC-MS. Febuxostat is an antihyperuricemic nonpurine inhibitor of both the oxidized and reduced forms of xanthine oxidase.¹ It inhibits bovine milk xanthine oxidase as well as mouse and rat liver xanthine oxidase/xanthine dehydrogenase (IC₅₀s = 1.4, 1.8, and 2.2 nM, respectively).² It is 10-30 times more potent than the hypoxanthine analog allopurinol .^3,4 Febuxostat decreases the serum level of urate in a potassium oxonate rat model of hyperuricemia (ED₅₀ = 1.5 mg/kg).² It reduces hepatic macrovesicular steatosis in mice fed a high-fat diet containing trans fatty acids when administered at a dose of 1 mg/kg per day.⁵ Febuxostat (0.75 mg/kg) also increases CNS expression of glutamate oxaloacetate transaminase 2 (GOT2) and improves neurological symptoms in a mouse model of secondary progressive experimental autoimmune encephalomyelitis (EAE).⁶ Formulations containing febuxostat have been used in the treatment of symptomatic hyperuricemia in patients with gout.

1.Okamoto, K., Eger, B.T., Nishino, T., et al.An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibitionJ. Biol. Chem.278(3)1848-1855(2003) 2.Osada, Y., Tsuchimoto, M., Fukushima, H., et al.Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodentsEur. J. Pharmacol.241(2-3)183-188(1993) 3.Takano, Y., Hase-Aoki, K., Horiuchi, H., et al.Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenaseLife Sci.76(16)1835-1847(2005) 4.Bisht, M., and Bist, S.S.Febuxostat: A novel agent for management of hyperuricemia in goutIndian J. Pharm. Sci.73(6)597-600(2011) 5.Nakatsu, Y., Seno, Y., Kushiyama, A., et al.The xanthine oxidase inhibitor febuxostat suppresses development of nonalcoholic steatohepatitis in a rodent modelAm. J. Physiol. Gastrointest. Liver Physiol.309(1)G42-G51(2015) 6.Honorat, J.A., Nakatsuji, Y., Shimizu, M., et al.Febuxostat ameliorates secondary progressive experimental autoimmune encephalomyelitis by restoring mitochondrial energy production in a GOT2-dependent mannerPLoS One12(11)e0187215(2017)