Febuxostat for the treatment of hyperuricemia in patients with gout

of disease process & therapeutic targets Hyperuricemia, as defined by a serum urate ≥6.8 mg/dl, is necessary but not sufficient to produce the clinical manifestations of gouty arthritis (gout) [1]. Hyperuricemia develops whenever there is a relative imbalance of production and excretion of urate. There are several other risk factors associated with the development of gout, mostly related to the effects on uric acid production or excretion. Common modifiable risk factors associated with increased uric acid production are obesity, high intake of meat and seafood and alcohol use, especially beer. Many drugs are associated with decreased uric acid excretion, including thiazide diuretics, low-dose aspirin and cyclosporine [2]. Therapeutic strategies for gout include treatment of inflammation and reduction of serum urate. There are three broad classes of drugs for urate-lowering therapy: xanthine oxidase (XO) inhibitors, uricosuric agents and the recombinant forms of the enzyme urate oxidase (uricase) [3]. XO inhibitors act by blocking the human enzyme XO. During purine metabolism, XO catalyzes the conversion of hypoxanthine to xanthine, and then xanthine to uric acid. Inhibition of XO leads to reduced levels of serum urate and increased levels of the more soluble precursor molecules, xanthine and hypoxanthine [4]. Allopurinol has been the classic XO inhibitor in use over the past 40 years, and has been recommended as a safe and costeffective therapy for long-term urate reduction in patients with gout [5]. While allopurinol is generally well-tolerated, its side-effect profile includes the possibility of allopurinol hypersensitivity syndrome, a rare but lifethreatening skin rash, which seems to be more common in patients with renal insufficiency [6]. In this article, we discuss the data on febuxostat, a novel XO inhibitor approved for urate reduction in patients with gout in the USA, Canada, Europe, South Korea and Japan.