Disease-Drug Interactions in Inflammatory States via Effects on CYP-Mediated Drug Clearance
David E Coutant1, Stephen D Hall1
1Department of Drug Disposition, Eli Lilly and Company, Indianapolis, IN, USA.
Abstract:
The human inflammatory response can result in the alteration of drug clearance through effects on drug-metabolizing enzymes or drug transporters. In this article, clinical examples are reviewed of how diseases with moderate to severe inflammation can decrease cytochrome P450 (CYP)-mediated drug clearance and alter plasma protein binding. Also examined is how albumin, α-1-acid glycoprotein, drug fraction unbound in plasma, CYP content, and oral clearance can change dynamically with time in response to inflammation.
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