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Induction of Hepatic Cytochrome P450 Enzymes: Importance in Drug Development and Toxicity

Throughout evolution mammals have developed a series of enzyme systems to detoxify xenobiotics (also termed foreign compounds) and hence promote their excretion from the body. The liver is the major site of xenobiotic metabolism in mammals of which the most important enzyme system is the cytochrome P450 (CYP) superfamily, which catalyses the oxygenation of a multitude of xenobiotics. Human, rat and mouse liver contain CYP enzymes in various subfamilies including CYP1A, CYP2A, CYP2B, CYP2C, CYP2D, CYP2E, CYP3A and CYP4A enzymes. The activities of many human and rodent hepatic CYP enzymes can be induced by a range of xenobiotics, although marked species differences are known to exist. Hepatic CYP enzyme induction normally occurs by receptor mediated mechanisms leading to an increase in gene transcription. In humans, the consequences of induction of CYP enzymes may result in clinically important drug–drug interactions, including organ transplant rejection, diminished antiretroviral effect, reduced anticoagulant effect and unplanned pregnancies. The induction of hepatic CYP enzymes by nongenotoxic agents in rodents may also be associated with tumour formation in the liver and other tissues (e.g. thyroid gland). Such effects in rodents are due to the mitogenic properties of the CYP enzyme inducers and are not relevant for humans.

Publication details

Print publication date
20 Nov 2015
Copyright year
Print ISBN
ePub eISBN
From the book series:
Drug Discovery