Regulation of drug metabolism and disposition during inflammation and infection

Area of Science:

• Pharmacology
• Biochemistry
• Immunology

Background:

• Cytochrome P450 (CYP) enzymes are crucial for drug metabolism.
• Infectious diseases and inflammation significantly alter CYP expression and activity.
• This alteration impacts the liver's and other organs' capacity to process xenobiotics and endogenous compounds.

Purpose of the Study:

• To explain how infections and inflammation affect drug metabolism.
• To highlight the role of cytokines and transcription factors in modulating CYP expression.
• To underscore the clinical implications of altered drug handling during disease states.

Main Methods:

• Review of existing clinical and preclinical data on CYP function during inflammation and infection.
• Analysis of the molecular mechanisms involving cytokines and transcription factors.
• Examination of pharmacokinetic changes reported in disease states.

Main Results:

• Inflammation and infection decrease the activity of major CYP forms.
• Cytokine production and altered transcription factor activity are key drivers of reduced CYP expression.
• Clinical evidence shows compromised drug clearance and altered pharmacokinetics in patients with inflammatory conditions or infections.

Conclusions:

• Altered CYP activity during infection and inflammation leads to impaired drug metabolism.
• Patients on CYP-metabolized drugs with a narrow therapeutic index are at high risk for adverse drug events.
• Understanding these changes is critical for safe and effective pharmacotherapy in clinical settings.