Regulation of drug-metabolizing enzymes and transporters in inflammation

Inflammation and infection have long been known to downregulate the activity and expression of cytochrome P450 (CYP) enzymes involved in hepatic drug clearance. This can result in elevated plasma drug levels and increased adverse effects. Recent information on regulation of human CYP enzymes is pres...

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Bibliographic Details
Published in:Annual review of pharmacology and toxicology 2006-01, Vol.46 (1), p.123-149
Main Authors: AITKEN, Alison E, RICHARDSON, Terrilyn A, MORGAN, Edward T
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carrier Proteins - metabolism
Cytochromes - metabolism
Gene Expression Regulation, Enzymologic - genetics
Gene Expression Regulation, Enzymologic - physiology
General pharmacology
Humans
Inflammation - enzymology
Inflammation - metabolism
Liver - metabolism
Medical sciences
Mixed Function Oxygenases - metabolism
Pharmaceutical Preparations - metabolism
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
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Summary:Inflammation and infection have long been known to downregulate the activity and expression of cytochrome P450 (CYP) enzymes involved in hepatic drug clearance. This can result in elevated plasma drug levels and increased adverse effects. Recent information on regulation of human CYP enzymes is presented, as are new developments in our understanding of the mechanisms of regulation. Experiments to study the effects of modulating CYP activities on the inflammatory response have yielded possible insights into the physiological consequences, if not the purpose, of the downregulation. Regulation of hepatic flavin monooxygenases, UDP-glucuronosyltransferases, sulfotransferases, glutathione S-transferases, as well as of hepatic transporters during the inflammatory response, exhibits similarities and differences with regulation of CYPs.
ISSN:0362-1642
1545-4304
DOI:10.1146/annurev.pharmtox.46.120604.141059