Probenecid with loop diuretics

The loop diuretics are rapidly absorbed. They are eliminated by the kidney by glomerular filtration and tubular secretion. Absorption of oral torsemide is more rapid (1 hour) than that of furosemide (2-3 hours) and is nearly as complete as with intravenous administration. The duration of effect for furosemide is usually 2-3 hours and that of torsemide is 4-6 hours. Half-life depends on renal function. Since loop agents act on the luminal side of the tubule, their diuretic activity correlates with their secretion by the proximal tubule. Reduction in the secretion of loop diuretics may result from simultaneous administration of agents such as NSAIDs or probenecid, which compete for weak acid secretion in the proximal tubule. Metabolites of ethacrynic acid and furosemide have been identified, but it is not known if they have any diuretic activity. Torsemide has at least one active metabolite with a half-life considerably longer than that of the parent compound. 

Loop diuretics exacerbate gout, because these drugs enter the tubule lumen through the organic acid secretory system. Because uric acid utilizes this system for transport into the renal tubule and subsequent elimination, competition exists for the transporter. This results in both increased levels of uric acid and increased plasma drug levels. In the same way, the drug interferes with the tubular secretion of probenecid, which is used in the therapy of gout. 

A comparative study" into the pharmacological mechanisms underlying the way drugs interfere with the actions of loop diuretics found that probenecid 1 g reduced the peak fractional excretion of sodium produced by a 6-mg dose of oral piretanide by 65%. Another study confirmed that probenecid reduces the natriuretic effects of piretanide. The clinical importance of these changes was not studied. 

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