Effects on Uric Acid Metabolism of the Drugs except the Antihyperuricemics

The normal adult male has a total body urate pool of approximately 1200 mg. Daily turnover of about 60 percent of the urate pool is achieved by balanced production and elimination of uric acid. About one-third of the human uric acid is derived from diet, while two-thirds is generated endogenously. The major site of purine synthesis is in the liver. The synthesis of uric acid occurs along two pathways, referred to as the de novo and the salvage pathways. Synthesis of the purine nucleotides begins with the formation of phosphoribosyl pyrophosphate (PRPP) by PRPP synthetase and leads to the first fully formed nucleotide, inosine 5’-monophosphate (IMP). IMP is converted into either adenosine 5’-monophosphate (AMP) or guanosine 5’-monophosphate (GMP) through two distinct reaction pathways. Catabolism of the purine nucleotides leads ultimately to the production of uric acid (Figure 1). On the other hand, about two-thirds of daily uric acid is excreted via the kidneys, and the remainder is excreted in feces. Many transport proteins are candidate participants in urate handling, with URAT1, GLUT9 and ABCG2 being the best characterized to date (Figure 2).