Higher therapeutic plasma oxypurinol concentrations might be required for gouty patients with chronic kidney disease

Lower dosages of allopurinol are recommended to avoid toxicity in gout patients with impaired renal function. This often has resulted in inadequate control of hyperuricemia. The optimum therapeutic range of plasma oxypurinol concentrations in gout patients with chronic kidney disease has never been investigated. This study was performed to examine the relationships between plasma oxypurinol concentrations and the changes in serum urate level and renal function after taking a standard dose of allopurinol, 300 mg daily, in gout patients with renal insufficiency.

The study was conducted in 27 gout patients with renal insufficiency in a rheumatology clinic at the Rajvithi Hospital, Bangkok. Both new and current patients, after they discontinued allopurinol completely for 4 weeks, were treated with allopurinol 300 mg daily for 6 weeks. Blood samples were collected immediately before and 5 hours after the studied dose had been taken. Serum urate levels and renal function were recorded before and after the 6 weeks of allopurinol treatments.

Most patients receiving allopurinol 300 mg/d had their plasma oxypurinol concentrations higher than the proposed therapeutic range for patients with normal renal function. There were significant relationships between changes in serum urate level with both trough and fifth-hour oxypurinol concentrations (R = 0.42, P = 0.002 and R = 0.27, P = 0.007, respectively). Higher plasma oxypurinol concentrations resulted in a higher percentage of patients who could meet the therapeutic treatment goal. No serious side effect and no significantly change in creatinine clearance were observed indicating that high levels of oxypurinol did not appear to relate to higher prevalence of adverse reaction.

Higher percentages of patients could meet the treatment goal when their plasma oxypurinol concentrations were higher than the proposed therapeutic range for patients with normal renal function.