The effects of endotoxemia and bacteremia on gastrointestinal drug absorption in mice and rats.

Endotoxin [lipopolysaccharide (LPS)] from four Gram-negative bacteria injected i.v. delayed absorption of drugs administered in solution by gastric tube to mice and rats. Salicylate and guinine absorption was delayed at LPS doses from 50 to 400 mug/kg. Salicylate absorption was delayed by LPS when drug was given by gastric tube, while LPS did not affect drug levels when salicylate was given i.p. or intraduodenally. Bethanechol prevented the LPS effect and LPS pretreatment also protected against delayed absorption. LPS- treated rats retained more drugs in their stomachs after 30 minutes and their plasma salicylate levels were lowered. Everted intestinal sacs from LPS-treated rats transferred salicylate as well as controls. Thus, LPS delays gastrointestinal drug absorption solely by retarding gastric emptying. Escherichia coli urinary tract infection did not reproduce LPS delay of drug absorption, but the effects of systemic bacteria were similar to those of endotoxemia.