Evaluation of the Optimal Dosage of Alopurinol in Japanese Patients

Abstract

Allopurinol is often used for the treatment of patients suffering from gout and hyperuricemia. However, adverse effects due to the accumulation of oxipurinol, the main active metabolite of allopurinol, have been reported in patients with renal insufficiency. Therefore, in order to prevent such adverse effects, some guidelines for the optimal dosage of allopurinol have been advocated. To evaluate these guidelines, the serum oxipurinol concentration in 101 patients with hyperuricemia treated with allopurinol was measured by HPLC. The serum oxipurinol concentration/dosage increased (p< 0.01) as the creatinine clearance level decreased. In addition, to evaluate the optimum dosage based on the renal function, Ccr was classified into three groups (Ccr≤30mL/min, 30mL/min<Ccr≤50mL/min, Ccr< 50mL/min).
A positive correlation was observed between the dosage of allopurinol and the serum oxipurinol concentration in each group (Ccr≤30mL/min, Ccr< 50mL/min : p< 0.01 30mL/min< Ccr : ≤50mL/min : p< 0.05).
Regarding the serum oxipurinol concentration/dosage in each group, it increased as the creatinine clearance level decreased (p< 0.05).
Based on our findings, the optimal dosages of allopurinol in each group in Japanese are considered to be as follows :
1) Ccr≤30mL/min : 50mg/day
2) 30mL/min< Ccr≤50mL/min : 100mg/day
3) Ccr< 50mL/min : 200mg/day