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The aims of this study were to determine factors that predict serum urate ( SU ) lowering response to allopurinol and the conversion of allopurinol to oxypurinol, and to determine a minimum therapeutic oxypurinol concentration. Data from 129 participants in a 24‐month open, randomized, controlled, parallel‐group, comparative clinical trial were analyzed. Allopurinol dose, SU, and plasma oxypurinol concentrations were available at multiple time points. The slope for the association between allopurinol dose and  SU  was calculated as a measure of sensitivity to allopurinol. The slope for the association between allopurinol dose and oxypurinol was calculated as a measure of allopurinol metabolism. Receiver operating characteristic ( ROC ) curves were used to identify a minimum oxypurinol concentration predictive of  SU  < 6 mg/dL. There was a wide range of SU concentrations for each allopurinol dose. The relationship between sensitivity to allopurinol and allopurinol metabolism for each 100 mg allopurinol dose increase varied between individuals. Body mass index ( P  = 0.023), creatinine clearance (Cr CL ;  P  = 0.037),  ABCG2  Q141K ( P  = 0.019), and  SU  ( P  = 0.004) were associated with sensitivity to allopurinol. The minimum oxypurinol concentration for achieving the urate target was found to be about 104 μmol/L, but predictive accuracy was poor ( ROC  curve area under the curve ( AUC ) 0.65). The minimum therapeutic oxypurinol concentration was found to increase with decreasing renal function. Although there is a positive relationship between change in oxypurinol and change in SU concentration, a minimum therapeutic oxypurinol is dependent on Cr CL  and cannot reliably predict SU target. Other variables, including   ABCG  2 Q141K genotype, impact on sensitivity to allopurinol ( ACTRN 12611000845932).

Relationships Between Allopurinol Dose, Oxypurinol Concentration and Urate‐Lowering Response—In Search of a Minimum Effective Oxypurinol Concentration