title: Measuring altered disposition of xenobiotics in experimental models of liver disease.
abstract: Understanding the metabolic pathway and excretion mechanisms governing the disposition of a compound is essential to the safe use of pharmaceutical agents. Because the liver is the primary organ responsible for the metabolism and elimination of xenobiotics, chronic liver disease can have a significant effect on the disposition of many xenobiotics due to changes in the expression or function of drug metabolizing enzymes and transporters. Liver disease can result in increased retention of a xenobiotic within the body, causing greater exposure of the individual to a potentially harmful compound, which may lead to toxicity. On the other hand, liver disease may also up-regulate the elimination processes of a xenobiotic, accelerating its removal from the body. With regard to a pharmaceutical agent, enhanced elimination may result in a decreased pharmacologic effect. Such alterations may necessitate dosage adjustments to achieve the desired therapeutic outcome.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, USA.
authors.forename: Rhiannon N
authors.initials: RN
authors.lastname: Hardwick
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Cherrington
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015262:Xenobiotics / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D015262:Xenobiotics