Pharmacology: Mechanism of action: Uric acid is the end product of purine metabolism in humans and is generated in the cascade of hypoxanthine → xanthine → uric acid. Both steps in the previous transformations are catalyzed by xanthine oxidase (XO). Febuxostat is a 2-arylthiazole derivative that achieves its therapeutic effects of decreasing serum uric acid by selectively inhibiting XO. Febuxostat is a potent, non-purine selective inhibitor of XO (NP-SIXO) with an in vitro inhibition Ki value less than one nanomolar. Febuxostat has been shown potently inhibit both the oxidized and reduced forms of XO. At therapeutic concentrations febuxostat does not inhibit other enzymes involved in purine or pyrimidine metabolism, namely, guanine deaminase, hypoxanthine guanine phosphoribosyltransferase, orotate phosphoribosyltransferase, orotidine monophosphate decarboxylase or purine nucleoside phosphorylase.
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