Pharmacokinetics
CYP450 Interactions
Cytochrome P450 enzymes in the liver metabolize most drugs. When an herb induces or inhibits a CYP enzyme, blood levels of any drug cleared by that enzyme shift — sometimes to toxic or subtherapeutic levels. St John's Wort is the most notorious; a handful of others are clinically relevant.
Reference
Major CYP enzymes and their herbal modulators
CYP3A4
Metabolizes ~50% of all drugs — most important interaction pathway.
- Inducers:
- St John's Wort (strong), echinacea (mild-moderate)
- Inhibitors:
- Goldenseal, grapefruit (not an herb but listed), black pepper (piperine, mild), milk thistle (weak), kava (moderate)
- Key drugs:
- Statins, immunosuppressants, oral contraceptives, many antivirals, most antidepressants
CYP2D6
Highly polymorphic — 10% of people are poor metabolizers at baseline.
- Inducers:
- Minimal herbal
- Inhibitors:
- Goldenseal, echinacea, St John's Wort
- Key drugs:
- Codeine → morphine conversion, tamoxifen, SSRIs (fluoxetine, paroxetine), tramadol, beta-blockers
CYP2C9
Warfarin is the canonical substrate.
- Inducers:
- St John's Wort (moderate)
- Inhibitors:
- Echinacea, goldenseal, milk thistle
- Key drugs:
- Warfarin, phenytoin, NSAIDs, some sulfonylureas
CYP2C19
PPI and antidepressant pathway.
- Inducers:
- St John's Wort
- Inhibitors:
- Ginkgo, kava, valerian (weak)
- Key drugs:
- PPIs (omeprazole), diazepam, clopidogrel activation, some antidepressants
CYP1A2
Smoking and cruciferous vegetables induce this — important for caffeine metabolism.
- Inducers:
- St John's Wort, broccoli/cruciferous food
- Inhibitors:
- Echinacea, chamomile (mild), cat's claw
- Key drugs:
- Caffeine, theophylline, clozapine, some antipsychotics, tizanidine
What this means practically
- Inducer = speeds metabolism = lowers drug level (drug stops working; risk of treatment failure).
- Inhibitor = slows metabolism = raises drug level (risk of toxicity).
- St John's Wort is a strong inducer of CYP3A4 and P-glycoprotein — it alone can cause failure of birth control, transplant drugs, HIV drugs, and blood thinners.
- Most CYP effects take 1-2 weeks to develop (induction) or resolve (days to weeks after stopping).