Febuxostat for Treatment of Chronic Gout

Charnelda L. Gray, Pharm.D., BCPS; Nafesa E. Walters-Smith, Pharm.D., BCPS


Am J Health Syst Pharm. 2011;68(5):389-398. 

In This Article


The therapeutic effect of febuxostat is achieved via the lowering of serum uric acid. The primary mechanism of action of febuxostat evaluated in trials was the inhibition of xanthine oxidase, evidenced by the increase in serum and urine xanthine concentrations, decrease in serum and urine uric acid levels, and lack of significant reduction in total purine synthesis.[2,10] In the purine metabolism cascade, xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid. Animal studies have demonstrated that febuxostat had a greater uric-acid-lowering effect than did allopurinol.[24,25] Febuxostat's chemical structure does not resemble a pyrimidine or purine and is unlike that of allopurinol.[26] It does not inhibit other enzymes involved in purine or pyrimidine metabolism. In vitro metabolism studies of febuxostat found no significant effect on the activity of cytochrome P-450 (CYP) isoenzymes 1A2, 92C9, 92C19, and 3A4.[27] Additional findings suggest that febuxostat may be a weak inhibitor of CYP2D6.[26,27] Mukoyoshi and colleagues[28] performed an in vitro examination of the effects of ibuprofen, verapamil, warfarin, and digoxin on the protein binding of febuxostat and found that these drugs minimally affected the binding of this novel agent and that febuxostat was unlikely to affect the plasma protein binding of warfarin and ibuprofen.[28] However, there was evidence that febuxostat decreased the protein binding of verapamil at high concentrations.


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