PMID: 3761200Oct 1, 1986Paper

Effect of prevention of inorganic sulfate depletion on the pharmacokinetics of acetaminophen in rats

The Journal of Pharmacology and Experimental Therapeutics
J H Lin, G Levy

Abstract

The elimination of large doses of acetaminophen is associated with substantial depletion of endogenous inorganic sulfate which is utilized for the formation of acetaminophen sulfate. This depletion has pronounced dose- and time-dependent effects on the pharmacokinetics of acetaminophen. The purposes of this investigation were to determine the pharmacokinetics of acetaminophen in rats when endogenous sulfate depletion is prevented by administration of inorganic sulfate and to develop a simple, physiologically based pharmacokinetic model for the elimination of acetaminophen under these conditions. Adult Sprague-Dawley rats received an i.v. injection and a continuous infusion of sodium sulfate as well as an i.v. injection of acetaminophen, either 15, 30, 150 or 300 mg/kg. Serum inorganic sulfate concentrations remained at or above the physiologic level at all times. Plasma concentrations of acetaminophen declined exponentially with time after the two lower doses but exhibited initial downward curvature in log-linear plots after the two larger doses. The time-averaged plasma clearance of acetaminophen decreased with increasing dose whereas the terminal half-life was dose-independent. Most of the drug was eliminated in the urine as ...Continue Reading

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