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Effect of aspirin on a subtoxic dose of 14C-acetaminophen in mice
Abstract:
The interaction of 14C-acetaminophen, 150 mg/kg (20 muCi/kg), and aspirin, 200 mg/kg po, was studied in male mice. The radiolabel was rapidly absorbed from the GI tract, achieving maximum blood levels 0.25 hr after oral dosing. Radioactivity in the blood equilibrated rapidly with the tissues and was concentrated in the liver and kidney. At 14 hr, most of the dose was eliminated in urine as the glucuronide, cysteine, sulfate, free drug, and mercapturate. Pretreatment with aspirin tended to reduce the rate and extent of acetaminophen absorption and altered the percentage of the dose excreted in the urine as sulfate, mercapturate, glucuronide, and cysteine. Interpretation of these data toxicologically as an indication of the potentiation of either toxicity or protection was not possible.
Insights
This study investigated how aspirin affects acetaminophen absorption and excretion in mice. Aspirin altered acetaminophen
Area of Science:
- Pharmacology and Toxicology
- Drug Metabolism and Pharmacokinetics
Background:
- Acetaminophen is a widely used analgesic and antipyretic.
- Drug interactions can alter the pharmacokinetic profiles of medications.
- Understanding these interactions is crucial for safe and effective drug use.
Purpose of the Study:
- To investigate the pharmacokinetic interaction between acetaminophen and aspirin in male mice.
- To determine the effect of aspirin pretreatment on acetaminophen absorption, distribution, metabolism, and excretion.
Main Methods:
- Male mice were administered radiolabeled acetaminophen (14C-acetaminophen) orally.
- Aspirin was administered orally prior to acetaminophen.
- Blood, urine, and tissue samples were collected at various time points.
- Radioactivity levels and acetaminophen metabolites were quantified.
Main Results:
- Acetaminophen was rapidly absorbed, with peak blood levels at 0.25 hours.
- Radioactivity distributed to liver and kidney tissues.
- Elimination occurred primarily via urine as glucuronide, cysteine, sulfate, free drug, and mercapturate conjugates within 14 hours.
- Aspirin pretreatment reduced acetaminophen absorption rate and extent.
- Aspirin altered the urinary excretion profile of acetaminophen metabolites.
Conclusions:
- Aspirin significantly impacts acetaminophen's absorption and metabolic excretion pathways in mice.
- The toxicological implications of this interaction, whether protective or potentiating, remain unclear based on this study.
- Further research is needed to elucidate the clinical significance of this drug interaction.