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

ABSTRACT

Introduction: 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
• transporters
• drug-diet interaction
• formulation

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Article highlights

• Piperine may affect the intestinal drug absorption process via the various mechanisms.

• Piperine can inhibit or stimulate the expression and functional activity of metabolic enzymes and drug transporters, depending on the administered doses, route of administration, and duration of treatment.

• Piperine may be used as a bioenhancer to improve the oral bioavailability of co-administered drugs.

• The concurrent use of piperine may cause clinically significant piperine-drug interactions, leading to therapeutic benefits or adverse effects.

• The development of effective formulations is critical to improve the bioavailability of piperine and, ultimately, to broaden the clinical applications of piperine.

This box summarizes key points contained in the article.

Additional information

Funding

This paper was supported by a grant (16173MFDS542) from Ministry of Food and Drug Safety and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2016R1A2B2010097).