Clinical pharmacology of drugs which influence uric acid production and excretion.

Abstract

The hyperuricemia which occurs in primary gout can be demonstrated in a large proportion of cases to be due to overproduction of uric acid, i.e., an increase in rate and amount of de novo biosynthesis. In myeloproliferative diseases there is also consistent overproduction of uric acid, in this case due to an exaggeration of cell “turnover” and degradation of nucleic acid purines. Several compounds are available which can increase the urinary excretion of uric acid with beneficial effects on chronic gout, both primary and secondary. The recent availability of allopurinol, an effective inhibitor of uric acid biosynthesis, provides a highly effective means for controlling hyperuricemia with less risk of toxicity and adverse effects than is present in the use of the uricosuric drugs. Other compounds are discussed which block uric acid excretion or increase uric acid biosynthesis. These are of interest from a pharmacologic standpoint and as models for the study of uric acid metabolism.