Effects of endotoxin derived from Escherichia coli lipopolysaccharide on the pharmacokinetics of drugs.

Lipopolysaccharide (LPS) endotoxin is an active component in the outer membrane of Gram-negative bacteria. LPS is usually used as an animal model of chronic inflammation such as sepsis. During inflammation, development of diarrhea, and changes in the plasma protein bindings, in the hepatic and/or intestinal microsomal cytochrome P450 (CYP) isozymes, and in the renal excretion of drugs have been reported. Thus, in rats pretreated with lipopolysaccharide endotoxin isolated from Escherichia Coli (ECLPS rats), the absorption, the distribution, the metabolism, and the excretion of drugs could be expected to alter. Interestingly, in ECLPS rats, the time-dependent effects on the hepatic CYP isozymes have been reported. Thus, in ECLPS rats, the pharmacokinetics of drugs which are mainly metabolized via hepatic CYP isozymes could be expected to be time-dependent. In this review, an attempt to explain changes in the pharmacokinetics of drugs reported in the literature was made in terms of hepatic CYP isozyme changes or urinary excretion changes in ECLPS rats.