Sulfate homeostasis. I. Effect of salicylic acid and its metabolites on inorganic sulfate in rats.
Homeostasis of inorganic sulfate, a physiologic anion necessary for both detoxification and biosynthetic reactions, involves predominantly capacity-limited renal clearance mechanisms. The objective of this investigation was to examine the effect of salicylic acid (SA) and its major metabolites, salicyluric acid and salicyl phenolic glucuronide, on the serum concentrations and renal clearance of inorganic sulfate in rats. Animals were studied using a crossover design in which they received a bolus i.v. injection (75 mg/kg) and infusion (approximately 0.26 mg/min/kg) of SA or the same volume of saline (the vehicle). Blood samples were collected at 2, 3 and 4 hr after administration and urine between 2 and 4 hr. The renal clearance of sulfate and creatinine were examined at mean steady-state SA serum concentrations of 249 micrograms/ml. Although no changes in the serum concentrations and renal clearance of creatinine were observed, the renal clearance of inorganic sulfate was increased significantly (2.13 +/- 0.74 vs. 1.09 +/- 0.54 ml/min/kg in controls, mean +/- S.D., n = 7) and its serum concentration decreased (0.55 +/- 0.12 vs. 1.04 +/- 0.23 mM in controls). These changes were not due to alterations in uric acid concentrations as uric acid serum concentrations and renal clearance were unchanged when examined at similar steady-state SA serum concentrations in a subsequent study. The effects on sulfate disposition also were probably not due to the major metabolites of SA: no changes in the serum concentrations or renal clearance of sulfate were observed at mean steady-state concentrations of 52 micrograms/ml of salicyluric acid or 73.7 micrograms/ml of salicyl phenolic glucuronide after their direct administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Morris
M E
ME
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Amherst.
Kwon
O
O
Mansfield
I L
IL
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005260:Female; D005965:Glucuronates / Q000494:pharmacology*; D006626:Hippurates / Q000494:pharmacology*; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000378:metabolism / Q000494:pharmacology*; D020156:Salicylic Acid; D013431:Sulfates / Q000493:pharmacokinetics*
D005965:Glucuronates; D006626:Hippurates; D012459:Salicylates; D013431:Sulfates; C000693:salicylurate; C049960:1-salicylate glucuronide; D020156:Salicylic Acid