ENHANCED PURINE SALVAGE DURING ALLOPURINOL THERAPY - AN IMPORTANT PHARMACOLOGIC PROPERTY IN HUMANS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 98  (5) , 673-683
Abstract
The contribution of enhanced purine salvage to the decreased total purine excretion associated with allopurinol therapy was measured by the i.v. administration of tracer doses of [8-14C]adenine to 4 patients with gout and normal purine salvage enzyme activity and 4 patients with Lesch-Nyhan syndrome and absent purine salvage activity. The mean cumulative excretion of radioactivity 5 days after the adenine administration to patients not receiving and receiving (off and on) allopurinol therapy was 6.1 and 3.6% of infused radioactivity for gouty subjects and 15.9 and 20.8% for the Lesch-Nyhan patients. Urate pool size and urate turnover, as measured by pool labeling with [2-14C]urid acid, were substantially decreased in both groups of patients during allopurinol therapy. Intestinal loss of uric acid was estimated from these pool measurements on and off allopurinol. With a correction for this extrarenal purine loss, the mean cumulative excretion of radioactivity 5 days after adenine administration to patients off and on allopurinol therapy were 11.9 and 4.8% for gouty subjects and 31.7 and 24.5% for the Lesch-Nyhan patients. In vitro studies demonstrated no alteration of the synthesis or degradation of adenine nucleotides by allopurinol in cultured human diploid fibroblasts. Evidently, enhanced purine salvage is an important component leading to decreased purine excretion during allopurinol therapy.