see also gout, pharmacology main index

• Uricosuric agents act directly on renal tubule → incr. uric acid renal excretion;
• They can also alter plasma binding, distribution & renal excretion of other organic acids;
• Uric acid in man generally demonstrates net reabsorption in most instances with about 10% of filtered uric acid being excreted, although net secretion is possible;
• This net reabsorption is via an inhibitable specific transporter which allows luminal uric acid to be exchanged with cellular anions (incl. PAH); The uric acid then exits cell via a different transporter on basolateral membrane not involving PAH;
• Uricosuric agents when present in lumen, compete with urate for the brush border transporter, thus decr. urate reabsorption;
• Probenecid also inhibits a specific PAH transporter on basolateral memb. → decr. i/cell. PAH & thus causing decr. PAH secretion;
• Biphasic effects on urate excretion are usually present depending on the concentration of the uricosuric agent.
  • Low doses usually cause decr. excretion presumably due to extreme sensitivity of urate secretion transporter to these drugs at the lower dose → decr. secretion & no effect on reabs.;
  • Higher doses usually incr. excretion as inhib. reabsorption » inhib. secretion;

• one drug may decr. tub. secret. of another drug → decr. luminal [] → decreased inhibition of urate reabsorption.
• inhib. of urate secretion by one drug may counter the inhib. of reabs. by another;

• Probenecid
• Sulfinpyrazone:
  • Strong organic acid congener of phenylbutazone with more potent uricosuric effect similar to probenecid, but lacks BTZ's anti-inflamm. effect although inhib. platelet function & may induce hypoglycaemia by decr. metabolism of sulfonyureas & also it inhibits metabolism of warfarin;