Optimizing therapy with allopurinol: factors limiting hypouricemic efficacy.
The aim of this review is to examine clinical aspects of the use of the hypouricemic drug allopurinol. Allopurinol is a moderately active hypouricemic drug. Its activity is largely the result of the inhibition of xanthine oxidoreductase by oxypurinol, the active metabolite of allopurinol. The activity of allopurinol may be limited by oxypurinol, reducing the renal clearance of urate. Optimal use of allopurinol involves individualization of dose to attain a sufficient decrease in plasma urate concentrations. This may require a dose greater than recommended based on creatinine clearance. The initial use of an anti-inflammatory drug or low-dose colchicine decreases but does not eliminate the development of acute attacks of gout during the initiation of therapy with allopurinol. Monitoring of oxypurinol concentrations has shed some light on the efficacy of allopurinol but more data are required particularly in patients with renal impairment. Probenecid increases the hypouricemic effect of allopurinol but the favorable interaction may be significant only in patients with glomerular filtration rates greater than about 50 mL/min.
Chung
Yewon
Y
Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia.
Stocker
Sophie L
SL
Graham
Garry G
GG
Day
Richard O
RO
D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D000963:Antimetabolites / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010117:Oxypurinol / Q000097:blood; D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians'; D014527:Uric Acid / Q000097:blood
D000963:Antimetabolites; D014527:Uric Acid; D000493:Allopurinol; D010117:Oxypurinol