PMID: 3753100Jun 1, 1986Paper

Effects of route of administration on the dose-dependent metabolism of acetaminophen in rats: relationship with its toxicity

Archives Internationales De Pharmacodynamie Et De Thérapie
P ColinS Chakrabarti

Abstract

The urinary metabolic excretion profile of acetaminophen (A) was reexamined in adult male Sprague-Dawley rats after administration of a single intraperitoneal (i.p.) or per oral (p.o.) dose of 100 or 750 mg/kg to 4 groups of animals, followed by collecting urines at 8, 24, 48 and 72 hr. The higher dose was administered in the form of a micronized suspension. The amounts of glucuronide, sulfate and mercapturate of A and unchanged A excreted in the urines were measured as a function of time. The pattern of urinary metabolic excretion of A was found to be dependent not only on the dose, but also on its route of administration as well as on the time of urine collection. When A was administered orally, the drug appears to be subjected to a gut and/or gut-wall first-pass elimination. The mean total urinary recovery of the drug was 70% after 72 hr following the administration of the higher dose of A. The hepatorenal toxicity was assessed by measuring the levels of serum glutamic-pyruvic transaminase activity and of urinary creatinine. The higher dose of A showed the potential to produce hepatic and renal toxicity when given i.p., but not when given orally. These toxic effects seem to be related with a high percentage of urinary A merc...Continue Reading

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