Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4

Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF · The Journal of Pharmacology and Experimental Therapeutics

Piperine inhibited P-glycoprotein-mediated transport of digoxin and cyclosporine (IC50 15.5 and 74.1 micromolar) and CYP3A4-mediated verapamil metabolism (Ki 36-77 micromolar), the two systems responsible for much of the first-pass elimination of orally administered drugs.

Population

Caco-2 cell monolayers and human liver microsomes

Intervention

Piperine

Comparator

Untreated cells and microsomes

Limitations

In vitro; the inhibitory concentrations are high relative to what a 5-20 mg supplemental piperine dose plausibly achieves systemically, which is why the human probe-drug study (pmid-22725836) found no clinical interaction.