Pharmacological Effects of 1,3,5-Triazines and Their Excretion Characteristics in the Rat

Abstract

Hyperuricemia is a metabolic and/or excretory disorder of purines associated with humans only. Thus the availability of experimental animal models for the study of human hyperuricemia has been very limited. In most mammalian species uric acid is converted to allantoin by uricase. Uricase is lacking in man and the apes. In these species uric acid rather than water-soluble allantoin is the end-product of purine metabolism (Fanelli³). To obtain an animal model for studies on hyperuricemia, hepatic uricase must be blocked with a selective inhibitor. Recently, use of the rat as a hyperuricemic animal model was described and subsequently used in different areas of research. Fridovich⁴ and Johnson¹ have shown that certain s-triazines are potent competitive inhibitors of uricase. Particularly oxonic acid and amide of oxonic acid have been described as effective inhibitors of uricase activity in vitro and in vivo. Since no studies have been carried out on their metabolism or excretion characteristics, the aim of this study was to examine the pharmacological effects and excretion characteristics of oxonic acid, amide of oxonic acid and of 5-azauracil in rats.