THE URICOSURIA AND OROTIC ACIDURIA INDUCED BY 6-AZAURIDINE*

Abstract

6-Azauridine is a pyrimidine analog which interrupts de novo pyrimidine biosynthesis by inhibiting the decarboxylation of orotidylic acid. Administration of this compound to bacteria, animals and humans has resulted in the excretion of orotic acid and orotidine in large quantities. The pattern of excretion of these compounds in 14 leukemic patients receiving 6-azauridine suggests a possible feedback control of pyrimidine biosynthesis in man. 6-Azauridine and orotic acid both are effective uricosuric agents when administered intravenously in man. Two- to three-fold increases in uric acid excretion and urate to inulin clearance ratios were noted after the infusion of 6-azauridine. Certain chemical structural similarities of these two compounds to uric acid suggest that they may represent a new class of uricosuric agents based on structural analogs of uric acid. There is no known role of pyrimidine coenzymes in the transport of urate.