Allopurinol in the Treatment of Gout

Abstract

The long term therapeutic use, safety and efficacy of allopurinol (4-hydroxypyrazolopyrimidine (3, 4-d) pyrim-idine), an inhibitor of xanthine oxidase, was investigated in 46 patients with gout. Thirty of the patients had severe disease poorly controlled with standard agents. Treatment was maintained for as long as 30 months in some individuals, and the average duration of therapy for the whole group was slightly over 12 months. Allopurinol was uniformly effective in lowering the serum uric acid concentration and the urine urate excretion to normal. Episodes of acute gouty arthritis continued to occur for several weeks but then gradually became less frequent, milder, and more responsive to symptomatic therapy. Disability associated with chronic arthritis became less and in most patients tophi gradually became smaller or disappeared. With the reduction in uric acid excretion the formation of urinary stones ceased. The therapeutic effect of allopurinol in 15 of the 16 patients with mild to moderately severe disease was good to excellent. Twenty of the thirty patients with severe disease had a good response, and seven a fair response. Drug reactions prevented therapeutic evaluation in 3 patients. Allopurinol was an exceptionally well tolerated drug, in general. Five patients with severe gout and impaired renal function developed a pruritic skin eruption, but chronic toxicity studies showed no evidence of hepatic, kidney, or bone marrow damage. The absorption and utilization of iron were unaffected. Patients with mild or moderately severe gout required 200 to 300 mg. of allopurinol daily for optimal control, and those with severe disease, 400 to 800 mg/day. Colchicine was used when necessary to prevent acute attacks. Probene cid and allopurinol were used together to increase renal clearance and the excretion of uric acid without evidence of drug incompatatiblity. Allopurinol appears to be a major addition to the existing therapeutic armamentarium for gout, particularly useful in the management of patients with severe disease, extensive tophaceous deposits, nephrop-athy, and in those who tend to form urate stones. It is a promising agent for the prevention of gouty nephropathy.