TIAPROFENIC ACID INHIBITS THE RENAL REABSORPTION OF SULFATE IN RATS

The objectives of the current investigation were: (1) to examine the effects of the nonsteroidal anti-inflammatory drug, tiaprofenic acid (TA), on sulfate renal reabsorption, and (2) to determine if concomitant prostaglandin E2 (PGE2) could reverse these effects. In crossover studies, female Lewis rats (n = 9) received either TA (as an intravenous (i.v.) bolus injection of 15 mg/kg and constant infusion of 0.02 mg/min) or its vehicle for 6 h. A blood sample was obtained at 5 h and urine was collected between 4 and 6 h. At a steady-state TA serum concentration of almost-equal-to 190 mug/ml, the PGE2 urinary excretion rate was inhibited by >90% with no change in glomerular filtration rate (GFR), as measured by creatinine clearance. TA administration resulted in a significant decrease in serum sulfate concentrations (0.65 +/- 0.22 vs 1.1 +/- 0.15 mM, mean +/- SD, p < 0.01) and increase in sulfate clearance ratio (0.32 +/- 0.14 vs 0.13 +/- 0.06, p < 0.01) when compared to the vehicle-treated period. There was also a significant decrease in the fraction of sulfate reabsorbed by the kidneys (0.68 +/- 0.14 vs 0.87 +/- 0.06 in the vehicle-treated period, p < 0.01). In a second crossover study, rats received either TA or TA plus PGE2. PGE2 was administered as an infusion (0.1 mug/min) beginning 210 min after the start of the TA infusion. An additional group of rats served as controls and received both vehicles. The fraction of sulfate reabsorbed was significantly increased (0.89 +/- 0.04 vs 0.82 +/- 0.02, p < 0.01, n = 6) and the sulfate clearance ratio was decreased (0.10 +/- 0.04 vs 0.18 +/- 0.03, p < 0.01, n = 6) following TA plus PGE2 when compared to TA treatment. Additionally, the fraction reabsorbed was significantly decreased and the clearance ratio was increased following TA treatment when compared to vehicle-treated controls; these parameters were not significantly different following TA plus PGE2 treatment when compared to controls. GFR was unchanged from the control value following TA or TA plus PGE2 treatment. The results of the current investigation suggest that renal PGs are involved in the renal reabsorption of sulfate.