Piperine-mediated drug interactions and formulation strategy for piperine: recent advances and future perspectives

Expert Opin Drug Metab Toxicol. 2018 Jan;14(1):43-57. doi: 10.1080/17425255.2018.1418854. Epub 2017 Dec 19.


Piperine has various pharmacological effects and can modulate the functional activity of metabolic enzymes and drug transporters. Consequently, there is a great interest in the application of piperine as an alternative medicine or bioavailability enhancer. Areas covered: This review deals with the effects of piperine on metabolizing enzymes and drug transporters. It provides the readers with an update on transporter-mediated and also metabolic enzyme-mediated piperine-drug interactions, with emphasis on its in vivo implications. This article also encompasses recent advances in the formulation approaches and technologies for optimizing the delivery of piperine. Expert opinion: Piperine can influence the pharmacokinetics of coadministered drugs, which may result in a therapeutically beneficial or adverse effect. Given that piperine inhibits or stimulates the activity of metabolic enzymes and transporters depending on the treatment conditions, the clinical significance of piperine-drug interactions should be assessed by varying the dose, dosing frequency, and the duration of treatment. In particular, better understanding the clinical relevance of piperine-drug interactions based on long-term assessments will provide a strong basis for the feasibility and applicability of piperine as a bioenhancer or a health-promoting agent. The development of effective formulations is also critical to facilitate the therapeutic applications of piperine.

Keywords: Piperine; drug metabolizing enzymes; drug-diet interaction; formulation; transporters.

Publication types

  • Review

MeSH terms

  • Alkaloids / administration & dosage*
  • Alkaloids / pharmacology
  • Animals
  • Benzodioxoles / administration & dosage*
  • Benzodioxoles / pharmacology
  • Biological Availability
  • Chemistry, Pharmaceutical / methods
  • Cytochrome P-450 Enzyme Inhibitors / administration & dosage*
  • Cytochrome P-450 Enzyme Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • Drug Interactions
  • Humans
  • Membrane Transport Proteins / drug effects
  • Membrane Transport Proteins / metabolism
  • Piperidines / administration & dosage*
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides / administration & dosage*
  • Polyunsaturated Alkamides / pharmacology


  • Alkaloids
  • Benzodioxoles
  • Cytochrome P-450 Enzyme Inhibitors
  • Membrane Transport Proteins
  • Piperidines
  • Polyunsaturated Alkamides
  • piperine