The liver primarily serves to help detoxify both endogenous and exogenous substances from the blood and intestines. Once blood from the intestines (delivered by the portal vein) or from the systemic circulation (delivered by the hepatic artery) enters the liver, it is filtered over liver cells called hepatocytes. Endogenous substances, such as bilirubin, and exogenous substances, such as drugs, are taken up by transporters on hepatocytes and undergo three phases of metabolism. The three phases allow the transported compound to be detoxified by a method of electron transfer (phase I), by addition of amino acid derivatives (phase II), and finally by exocytosis from the hepatocyte into the bile (phase III). The bile is then transported into the small intestine, and finally excreted from the body.
Amino acid derivatives are often taken from the Krebs cycle, added to sugar nucleotides, and transferred to molecules for detoxification. A common example of an enzyme responsible for this is UDP-glucuronosyl transferase.
A decrease in the extraction of a drug by the liver may be observed under which of the following conditions?