Regulation of drug metabolism and disposition during inflammation and infection

Abstract

The expression and activity of cytochrome P450 (CYP) is altered during periods of infectious disease or when an inflammatory response is activated. Most of the major forms of CYP are affected in this manner and this leads to a decrease in the capacity of the liver and other organs to handle drugs, chemicals and some endogenous compounds. The loss in drug metabolism is predominantly an effect resulting from the production of cytokines and the modulation of the transcription factors that control the expression of specific CYP forms. In clinical medicine numerous examples have been reported indicating the occurrence of compromised drug clearance and changes to pharmacokinetics during disease states with an inflammatory component or during infections. For any drug that is metabolised by CYP and has a narrow therapeutic index, there is a significant risk in placing patients in a position where an infection or inflammatory response might lead to aberrant drug handling and an adverse drug response.

Keywords::

• cytochrome P450
• drug disposition
• drug metabolism
• drug toxicity
• infection
• inflammation