Endotoxin and pharmacokinetics of rifampicin

Changes of pharmacokinetics of rifampicin (20 mg . kg-1 orally) were seen in rabbits pretreated with 0.02, 0.2 and 2.0 micrograms . kg-1 of endotoxin S. typhimurium given intravenously. The animals served as their own controls. The two higher endotoxin doses induced significantly lower plasma levels and changes in the absorption and elimination phase. After the lowest endotoxin dose the results were variable. Tolerance to pyrogenicity of endotoxin, produced by daily toxin administration abolished the otherwise induced changes in rifampicin pharmacokinetics.