Amphotericin B fever in rabbits.

Area of Science:

• Pharmacology
• Toxicology
• Immunology

Background:

• Amphotericin B (amB) is a critical antifungal agent.
• Fever is a common side effect of intravenous drug administration.
• Understanding pyrogenic responses to amB is crucial for patient safety.

Purpose of the Study:

• To investigate the pyrogenic effects of amphotericin B (amB) in rabbits.
• To compare fever induction by slow infusion versus bolus injection of amB.
• To determine the threshold pyrogenic dose of amB in rabbits.

Main Methods:

• Intravenous administration of amphotericin B (amB) to male adult rabbits via slow infusion and bolus injection.
• Dose-ranging studies to identify pyrogenic thresholds.
• Assessment of rectal temperature changes.
• Evaluation of amB pyrogenicity in endotoxin-tolerant rabbits and mice.

Main Results:

• Slow intravenous infusion of amB induced a moderate, dose-dependent fever in rabbits.
• Bolus injection of amB was less pyrogenic, requiring higher doses for fever induction.
• The threshold pyrogenic dose of amB was approximately 0.16 mg/kg.
• Endotoxin-tolerant rabbits exhibited a blunted febrile response to amB.
• No fever was observed in mice treated with amB.

Conclusions:

• The route and rate of amphotericin B administration significantly influence its pyrogenic potential in rabbits.
• Fever response to amB is dose-dependent and can be modulated by endotoxin tolerance.
• Amphotericin B does not appear to be pyrogenic in mice.