No abstract

in solution at the usual pH of urine.19 Therefore, we have recommended a large fluid intake and the ingestion of about 8 gm. of sodium bicarbonate daily during pro¬ benecid therapy. When the initial serum uric acid level is very high, it is probably safer to begin treatment at 1 gm. of probenecid per day. However, we have had no experience with that dosage.The failure of probenecid therapy to lower the serum urate level in three patients with diminished renal func¬ tion must be further explored in both gouty and nongouty patients. It is important to determine whether renal in¬ sufficiency was actually the cause of failure of probenecid action in these cases and, if so, what the nature and de¬ gree of the renal defect must be to cause this failure. Such experiments are now being carried out. SUMMARYThe therapeutic potentialities of probenecid in the treatment of recurrent gout and chronic gouty arthritis were studied in 20 patients. Ten were followed for periods of five to seven and a half months. With a dose of 2 gm. daily, serum uric acid fell within 72 hours to an average of 55% of the control level. This was associated with an initial increase in urate excretion of 35% to 200%.Urate clearances remained increased two to fourfold with continued probenecid administration.In three patients with decreased renal function, pro¬ benecid therapy produced no fall in the serum uric acid level. When acetylsalicylic acid was given simultaneously with probenecid, the action of the latter in lowering the serum uric acid level was completely annulled but was restored when acetylsalicylic acid therapy was discon¬ tinued.Probenecid therapy proved of greatest benefit in chronic gouty arthritis. Joint movement improved prog¬ ressively in all patients; pain and swelling subsided. Acute attacks of gout developed in some patients soon after treatment was started, but their incidence diminished with continued therapy. No significant or consistent changes occurred in the serum electrolyte concentrations during prolonged therapy. No abnormalities in blood cell distribution were found. Results of hepatic and renal function tests remained normal. In one patient mild hematuria occurred from urate crystals during the first stage of treatment.