P-glycoprotein inhibition
P-glycoprotein inhibition. Blocks the efflux pump that ejects drugs back into the gut lumen and out of the brain. Raises absorption of P-gp substrates like digoxin, and can raise brain exposure independently of blood level.
P-glycoprotein induction. Increases the efflux pump, lowering absorption. St John's wort does this and CYP3A4 induction at the same time — two mechanisms pointing the same way.
What acts on it
- Grapefruit — inhibits, weak
- Black pepper (piperine) — inhibits, moderate
- St John's wort
— induces, strong
Johne et al. measured reduced digoxin exposure with hypericum extract. - Ketoconazole / itraconazole — inhibits, strong
- Rifampicin (rifampin) — induces, strong
- Amiodarone — inhibits, strong
What is affected by it
- Ciclosporin / tacrolimus (narrow therapeutic index)
- Digoxin (narrow therapeutic index)
What a clean result means here
A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.
In this dataset
- Monoamine oxidase inhibition (prescription MAOIs, RIMAs, linezolid, methylene blue, harmala alkaloids)
- Serotonergic drugs and the serotonin-toxicity mechanism
- Dietary tyramine and L-dopa loads
- The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
- P-glycoprotein inhibition and induction
- 11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
- QT prolongation as an additive pharmacodynamic axis
- Culinary seasonings and common foods with documented pharmacological activity
- A selected set of narrow-therapeutic-index drugs where those shifts matter most
Not in this dataset
- Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
- Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
- Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
- Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
- Renal and hepatic impairment, age, pregnancy, and body composition.
- Additive sedation, respiratory depression, bleeding risk, hypoglycaemia and most other pharmacodynamic axes beyond the ones listed above.
- Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
- Allergy, intolerance, and contamination or adulteration of unregulated products.
- Anything published after the last-reviewed date below.
72 substances, 20 mechanisms, 64 citations. Last reviewed . Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.
References
- Bailey DG, Dresser G, Arnold JMO (2013). Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?. CMAJ (published online 2012-11-26). doi:10.1503/cmaj.120951
- Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF (2002). Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4. The Journal of Pharmacology and Experimental Therapeutics. doi:10.1124/jpet.102.034728
- Johne A, Brockmöller J, Bauer S, Maurer A, Langheinrich M, Roots I (1999). Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clinical Pharmacology & Therapeutics. doi:10.1053/cp.1999.v66.a101944
- U.S. Food and Drug Administration (2023). Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. FDA. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned title checked against the one printed here. Three DOIs in the first draft resolved to real but different papers and were corrected before publication.
Last reviewed . All interaction pages.