Drugs affecting hepatic enzymes

• the cytochrome P450 system is a group of enzymes that control the concentrations of many endogenous substances and drugs. These enzymes are mainly found in the liver (hepatic microsomal enzymes) and gut
• cytochrome P450 system is comprised of about 40-50 isoenzymes. Each isoenzyme is derived from the expression of an individual gene
  
  
• originally the system was identified as a pigment in hepatic microsomes. When examined, the pigment had a characteristic spectrophotometric profile with an associated peak at 450nm (hence the term cytochrome P450 system)
  
  
• the main effect of the cytochrome P450 enzymes is to catalyse oxidation, which generally makes the substrate more water-soluble and so more readily excreted by the kidneys
  
  
• of the many isoenzymes in the cytochrome P450 system, only a few appear to be responsible for the metabolism of commonly used drugs (CYP 1A2, CYP 2C9, CYP 2C19, CYP 2D6, CYP 3A3, CYP 3A4)
  
  
• the metabolism of drugs that are inactivated by the cytochrome P450 enzymes can be altered by substances which either induce these enzymes and therefore increase degradation, or substances that inhibit these enzymes and therefore are associated with increased levels of the drug
  
  
• dietary components can also affect the cytochrome P450 system:
  • grapefruit juice is believed to inhibit the activity of CYP 3A4 in the small bowel epithelium (1)
  • charcoal-grilled food and cruciferous vegatables (e.g. cauliflower, cabbage, broccoli) induce the cytochrome P450 enzymes
    
    
• smoking induces CYP 1A2 activity and hence reduces plasma levels of drugs metabolised by this enzyme e.g. fluvoxamine (2)

Reference:

• 1) Walter-Sack I, Klotz U (1996). Influence of diet and nutritional status on drug metabolism. Clin Pharmacokinetics, 31, 47-64.
• 2) Spigset O et al (1995). Effect of cigarette smoking on fluvoxamine pharmacokinetics in humans. Clin Pharmacol Ther, 58, 399-403.