Orally administered thiazides are rapidly absorbed from the gastrointestinal tract and begin to produce diuresis in about 1 hour. Approximately 50% of an oral dose is excreted in the urine within 6 hours. These compounds are organic acids and are actively secreted into the proximal tubular fluid by the organic acid secretory mechanism. There also appears to be an extrarenal pathway for their elimination involving the hepatic-biliary acid secretory system that is particularly important for thiazide elimination when renal function is impaired.
The thiazides have a variable effect on elimination of uric acid, which also is secreted by the renal acid secretory mechanism. Administration of thiazide diuretics, especially at low doses, may elevate serum uric acid levels and cause goutlike symptoms. Following large doses, thiazides may compete with uric acid for active reabsorption and thereby may promote uric acid elimination rather than impair it (see Chapter 37).
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