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Acetaminophen has greater antipyretic efficacy than aspirin in endotoxemia: a randomized, double-blind,
T Pernerstorfer1, R Schmid, C Bieglmayer
1Department of Clinical Pharmacology, TARGET, Vienna University Hospital School of Medicine, Austria.
Objective:
To compare the antipyretic efficacy of aspirin and acetaminophen (INN, paracetamol) in 30 male volunteers with the use of endotoxin (lipopolysaccharide) to elicit a standardized febrile response.
Methods:
A randomized, double-blind, placebo-controlled trial was conducted in parallel groups. Subjects received an intravenous endotoxin bolus of 4 ng/kg after premedication with either placebo, 1000 mg aspirin, or 1000 mg acetaminophen by mouth.
Results:
Peak body temperatures were 38.5 degrees C +/- 0.2 degrees C in the placebo group, 37.6 degrees C +/- 0.2 degrees C in the acetaminophen group (P = .001 versus placebo), and 38.6 degrees C +/- 0.2 degrees C in the subjects treated with aspirin (P = .001 versus acetaminophen; P = .570 versus placebo) at 4 hours after lipopolysaccharide infusion. Subjective symptom scores for chills and perception of fever were higher in the placebo group than in the acetaminophen group (chills, 2.5 +/- 0.3 versus 1.0 +/- 0.2, P = .009 and fever, 2.5 +/- 0.2 versus 2.0 +/- 0.2, P = .021). Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 levels rose by several orders of magnitude (P < .001 versus baseline in all groups), without significant intergroup differences.
Conclusions:
Acetaminophen was the superior antipyretic drug in endotoxemia compared with aspirin. Treatment with acetaminophen ameliorates subjective symptoms induced by endotoxemia without compromising the humoral response of a subject to endotoxin. This observation has clinical interest and may also help to improve the lipopolysaccharide model, which can be used to test anti-inflammatory and anticoagulatory drugs.
Insights
Acetaminophen effectively reduced fever in endotoxemia compared to aspirin. This study highlights acetaminophen
Area of Science:
- Pharmacology
- Immunology
- Clinical Medicine
Background:
- Fever is a common symptom of infection and inflammation.
- Antipyretic drugs like aspirin and acetaminophen are widely used to reduce fever.
- Endotoxin models provide a standardized method to study fever and drug efficacy.
Purpose of the Study:
- To compare the antipyretic efficacy of aspirin and acetaminophen.
- To evaluate the effects of these drugs on subjective fever symptoms.
- To assess the impact of these antipyretics on the humoral immune response to endotoxin.
Main Methods:
- A randomized, double-blind, placebo-controlled trial was conducted.
- 30 male volunteers received endotoxin (lipopolysaccharide) to induce fever.
- Participants were treated with placebo, 1000 mg aspirin, or 1000 mg acetaminophen.
Main Results:
- Acetaminophen significantly reduced fever compared to placebo (P = .001).
- Aspirin did not show significant antipyretic effect compared to placebo (P = .570).
- Acetaminophen improved subjective symptoms of chills and fever perception.
Conclusions:
- Acetaminophen is a superior antipyretic agent compared to aspirin in endotoxemia.
- Acetaminophen alleviates endotoxin-induced symptoms without impairing the humoral response.
- This study validates the endotoxin model for evaluating anti-inflammatory and anticoagulatory drugs.