Acetaminophen has greater antipyretic efficacy than aspirin in endotoxemia: A randomized, double-blind, placebo-controlled trial

Abstract

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°C ± 0.2°C in the placebo group, 37.6°C ± 0.2°C in the acetaminophen group (P = .001 versus placebo), and 38.6°C ± 0.2°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–α, 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. Clinical Pharmacology & Therapeutics (1999) 66, 51–57;