PLASMA-CLEARANCE IN THE RAT OF A FURAN DICARBOXYLIC-ACID WHICH ACCUMULATES IN UREMIA

The furan dicarboxylic acid 3-carboxylic-4-methyl-5-propyl-2-furanprop anoic acid (5-propyl FPA) accumulates in the plasma of patients with c hronic renal failure and has been implicated in several aspects of the uremic syndrome: the defective binding of organic acids in uremic pla sma, inhibition of active tubular secretion, anemia and the severity o f neurological symptoms. Evidence from experiments with rat kidney sli ces suggests that 5-propyl FPA undergoes active tubular secretion, and so its clearance after an intravenous bolus dose (5 mg/kg; 21 mu mol/ kg) was investigated in anaesthetized female Wistar albino rats in viv o. The effects of intravenous bolus doses of p-aminohippuric acid (PAH ) and probenecid on the clearance of this dose of 5-propyl FPA were al so studied. The mean values (N = 16) for plasma half-life, plasma clea rance and apparent volume of distribution of 5-propyl FPA were 3.6 hou rs, 2.4 ml . min(-1). kg(-1) and 0.69 liter . kg(-1), respectively. An equimolar dose of PAH did not affect the clearance of 5-propyl FPA, b ut a tenfold higher molar dose of PAH (40.4 mg/kg) increased the area under the plasma-concentration time curve of 5-propyl FPA, and there w as a trend towards a decrease in the clearance and a prolongation of t he half-life. Probenecid at a fivefold higher dose than 5-propyl FPA h ad a similar effect to PAH and increased the AUC of 5-propyl FPA. PAH and probenecid decreased the plasma clearance of 5-propyl FPA, which i s evidence that this uremic metabolite undergoes active tubular secret ion. It follows that 5-propyl FPA could therefore inhibit the secretio n of other organic acids.