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- W2045333028 abstract "□ Certain drugs that are eliminated partly by conjugation with sulfate cause appreciable depletion of endogenous inorganic sulfate in animals and humans. The limited availability of endogenous inorganic sulfate contributes to, or is responsible for, dose-dependent elimination kinetics and can cause pronounced time-dependent changes in the disposition of drugs that are metabolized to sulfate conjugates. A comprehensive characterization of the pharmacokinetics of such drugs requires, therefore, an interdigitation with the kinetics of endogenous inorganic sulfate. The latter is cleared from the body primarily by renal excretion. The purpose of this investigation was to determine the relationship between the renal clearance and the serum concentration of inorganic sulfate, particularly in the subnormal concentration range during acet-aminophen-induced sulfate depletion. Administration of acetaminophen, 150 mg/kg iv, to adult male rats reduced their serum inorganic sulfate concentration from≃1 mM to <0.1 mM without affecting the renal clearance of creatinine. The renal clearance ratio, sulfate–creatinine, decreased from between 0.2 and 0.3 at≃1 mM serum sulfate to≃0.05 at <0.1 mM serum sulfate concentration. When serum sulfate concentration was increased to≃1.5 mM by iv infusion of sodium sulfate, the sulfate–creatinine renal clearance ratio increased abruptly to≃1 without affecting creatinine renal clearance. Acetaminophen had no effect on the high renal clearance of inorganic sulfate during hypersulfatemia. The pronounced serum concentration dependence of sulfate renal clearance facilitates inorganic sulfate homeostasis. A survey of the literature indicates that the relatively low endogenous serum sulfate concentration (≃0.3–0.4 mM) in humans (compared with dogs, rabbits, and rats) is due primarily to low formation rate rather than high renal clearance of inorganic sulfate." @default.
- W2045333028 created "2016-06-24" @default.
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- W2045333028 date "1983-03-01" @default.
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- W2045333028 title "Renal Clearance of Inorganic Sulfate in Rats: Effect of Acetaminophen-Induced Depletion of Endogenous Sulfate" @default.
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- W2045333028 doi "https://doi.org/10.1002/jps.2600720303" @default.
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