title: Xanthine oxidoreductase and its inhibitors: relevance for gout.
abstract: Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism and converts hypoxanthine to xanthine, and xanthine into uric acid. When concentrations of uric acid exceed its biochemical saturation point, crystals of uric acid, in the form of monosodium urate, emerge and can predispose an individual to gout, the commonest form of inflammatory arthritis in men aged over 40 years. XOR inhibitors are primarily used in the treatment of gout, reducing the formation of uric acid and thereby, preventing the formation of monosodium urate crystals. Allopurinol is established as first-line therapy for gout; a newer alternative, febuxostat, is used in patients unable to tolerate allopurinol. This review provides an overview of gout, a detailed analysis of the structure and function of XOR, discussion on the pharmacokinetics and pharmacodynamics of XOR inhibitors-allopurinol and febuxostat, and the relevance of XOR in common comorbidities of gout.
authors: Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Darlinghurst 2010, Sydney, Australia r.day@unsw.edu.au.|St Vincent's Clinical School, UNSW Australia, Darlinghurst 2010, Sydney, Australia.|School of Medical Sciences, UNSW Australia, Kensington 2052, Sydney, Australia.
authors: Richard O
authors: RO
authors: Day
authors: Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Darlinghurst 2010, Sydney, Australia.|School of Medical Sciences, UNSW Australia, Kensington 2052, Sydney, Australia.
authors: Bishoy
authors: B
authors: Kamel
authors: Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Darlinghurst 2010, Sydney, Australia.|School of Medical Sciences, UNSW Australia, Kensington 2052, Sydney, Australia.
authors: Diluk R W
authors: DR
authors: Kannangara
authors: Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Darlinghurst 2010, Sydney, Australia.|School of Medical Sciences, UNSW Australia, Kensington 2052, Sydney, Australia.
authors: Kenneth M
authors: KM
authors: Williams
authors: Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Darlinghurst 2010, Sydney, Australia.|School of Medical Sciences, UNSW Australia, Kensington 2052, Sydney, Australia.
authors: Garry G
authors: GG
authors: Graham
mesh_terms: D000493:Allopurinol / Q000008:administration & dosage; D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D000069465:Febuxostat / Q000008:administration & dosage; D006073:Gout / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D006074:Gout Suppressants / Q000008:administration & dosage*; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D000069465:Febuxostat; D014527:Uric Acid; D019271:Hypoxanthine; D000493:Allopurinol; D014968:Xanthine Dehydrogenase
keywords: allopurinol; febuxostat; gout; reactive oxidative species; uric acid; xanthine oxidoreductase