Cytochrome P450
The body's chemical processing plant. Cytochrome P450 (CYP) enzymes metabolize the majority of drugs, toxins, and hormones. Located mainly in the liver, they perform Phase I detoxification. Genetic variants make some people fast or slow metabolizers—affecting drug response, caffeine tolerance, and toxin clearance.
Key CYP450 Enzymes
CYP3A4
Metabolizes ~50% of drugs. Statins, calcium blockers, many others. Grapefruit inhibits.
CYP2D6
~25% of drugs. Antidepressants, codeine, tamoxifen. Highly polymorphic.
CYP1A2
Caffeine, theophylline. Smoking induces it. Vegetables affect activity.
CYP2C19
PPIs, clopidogrel, antidepressants. Common polymorphisms. Asian populations differ.
CYP2C9
Warfarin, NSAIDs, sulfonylureas. Variants affect warfarin dosing critically.
CYP2E1
Alcohol, acetaminophen. Induced by alcohol. Generates toxic intermediates.
Metabolizer Phenotypes
Poor Metabolizer
Little to no enzyme activity. Drugs accumulate. Higher side effect risk. Need lower doses.
Intermediate
Reduced function. Between normal and poor. May need dose adjustments.
Normal (Extensive)
Standard function. Standard drug dosing typically appropriate.
Ultra-Rapid
Multiple gene copies. Clears drugs too fast. May need higher doses or fail to respond.
Inducers & Inhibitors
Common Inhibitors (Slow CYP)
Grapefruit juice (CYP3A4), cimetidine, fluoxetine, ketoconazole. Increase drug levels.
Common Inducers (Speed CYP)
Smoking, St. John's Wort, rifampin, carbamazepine, cruciferous vegetables. Decrease drug levels.
Clinical Implications
Pharmacogenomic Testing
Test before certain drugs. Warfarin, clopidogrel, codeine, tamoxifen especially.
Drug Interactions
Multiple drugs using same CYP compete. One may increase levels of another.
Food Interactions
Grapefruit, pomelo, Seville oranges. Can dramatically affect drug levels.
Supplement Interactions
St. John's Wort induces CYPs. Can reduce birth control, HIV med effectiveness.
Caffeine Sensitivity
CYP1A2 slow metabolizers sensitive. Fast metabolizers need more for effect.
Hormone Metabolism
Estrogens processed by CYPs. Affects hormone balance, cancer risk pathways.