Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics

• Authors: Edward T Morgan, Emory University
• Journal Title: Clinical Pharmacology and Therapeutics
• Volume: Volume 85, Number 4
• Publisher: American Society for Clinical Pharmacology and Therapeutics | 2009-04, Pages 434-438
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/clpt.2008.302
• Subjects: Health Sciences, Pharmacology
• Keywords: drug metabolism; pharmacokinetics; inflammation; infection; cytokines; biologics

Abstract

Infection and inflammation are associated with down-regulations of hepatic and extrahepatic cytochrome P450s, as well as other drug metabolizing enzymes and transporters. We will review the genesis of inflammatory reactions, and discuss the relevance of the inflammatory regulation of P450 enzymes observations to clinical drug-disease and drug-drug interactions. Mechanistically, understanding the enzyme specificity and mechanisms of regulation will allow us to make better decisions about drug dosage regimens when a patient’s inflammatory status changes.