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 approximately 190 micrograms/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 micrograms/min) beginning 210 min after the start of the TA infusion. An additional group of rats served as controls and received both vehicles.(ABSTRACT TRUNCATED AT 250 WORDS)
Benincosa
L J
LJ
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, Amherst.
Morris
M E
ME
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001693:Biological Transport, Active; D003404:Creatinine / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013431:Sulfates / Q000097:blood / Q000378:metabolism* / Q000652:urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; D013431:Sulfates; C021270:tiaprofenic acid; D003404:Creatinine; D015232:Dinoprostone