Rationale:

• Tissue uric acid deposits can be eliminated only if the concentration gradient between the tissues and serum is sufficient.

Evidence:

• Monosodium urate solubility in Na⁺, 140 mg/dL, is 6.8 mg/dL at 37°C, 6.0 mg/dL at 35°C, and at 4.5 mg/dL at 30^oC. The temperature of the distal extremities is less than the core temperature; this may facilitate deposition of monosodium urate crystals in soft tissues and joints (53).
• In an observational study, the risk for a gout attack during uric acid-lowering therapy was 30% less if the uric acid level was maintained between 4.5 and 6.6 mg/dL; a relatively slow decrease in uric acid values of 0.1 to 0.6 mg/dL in the first month also resulted in fewer acute gout attacks (54).
• A trial of withdrawal of urate-lowering medications followed patients with urate-lowering therapy for 5 years with no palpable tophi and a mean uric acid level during that time of < 7 mg/dL. Forty-two percent of patients had a recurrence from 6 to 60 months after urate-lowering therapy had been discontinued. Uric acid levels returned to the level before urate-lowering therapy (mean of 9 mg/dL). Predictors of flare included higher urate levels both during therapy and after therapy had been withheld (55).

Comments:

• Sulfinpyrazone may also be used as a uricosuric agent; however, it has significant effects on the kidney and GI tract that are similar to those of NSAIDs. Therefore, its use in patients with renal disease may be inadvisable.
• Uricosurics such as probenecid and sulfinpyrazone promote excretion of oxypurinol, the major active metabolite of allopurinol, and concomitant use of these drugs may reduce the uric acid lowering effect of allopurinol.