The influence of piperine on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy volunteers

Eur J Clin Pharmacol. 2017 Mar;73(3):343-349. doi: 10.1007/s00228-016-2173-3. Epub 2016 Dec 15.


Purpose: Piperine (PIP) has been found to inhibit P-glycoprotein (P-gp) function in rats, suggesting that it may have the potential to modulate P-gp-mediated drug efflux in humans. The aim of this study was to evaluate the effect of PIP on the pharmacokinetics of fexofenadine (FEX), a P-gp substrate, in healthy volunteers.

Methods: An open-label, two-period, sequential study involving 12 healthy volunteers was conducted. A single oral dose of FEX 120 mg was given to volunteers during the control phase and after the treatment phase. A once-daily oral dose of PIP 20 mg was given to volunteers during the treatment phase (10 days). Blood samples were collected at predefined time intervals, and plasma samples containing FEX were analyzed by liquid chromatography-tandem mass spectrometry.

Results: Treatment with PIP significantly increased maximum plasma concentration of FEX [406.9 (control) vs. 767 ng/mL (treatment)] and area under the plasma concentration-time curve [3403.7 (control) vs. 5724.7 ng.h/mL (treatment)] when compared to the control phase. In contrast, PIP treatment significantly decreased apparent oral clearance of FEX [35.4 (control) vs. 20.7 L/h (treatment)] as compared to the control. There was no significant change observed in the half life and renal clearance of FEX between the treatment phase and control phase.

Conclusions: The results suggest that altered pharmacokinetics and enhanced bioavailability of FEX might be attributed to PIP-mediated inhibition of P-gp drug efflux. Therefore, intake of PIP or dietary supplements containing PIP may potentially enhance the absorption or bioavailability of P-gp substrate drugs in addition to FEX.

Keywords: Bioavailability; Fexofenadine; P-glycoprotein; Pharmacokinetics; Piperine.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects*
  • Adult
  • Alkaloids / pharmacology*
  • Area Under Curve
  • Benzodioxoles / pharmacology*
  • Biological Availability
  • Half-Life
  • Healthy Volunteers
  • Histamine H1 Antagonists, Non-Sedating / pharmacokinetics*
  • Histamine H1 Antagonists, Non-Sedating / pharmacology
  • Humans
  • Male
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • Terfenadine / analogs & derivatives*
  • Terfenadine / pharmacokinetics
  • Terfenadine / pharmacology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Alkaloids
  • Benzodioxoles
  • Histamine H1 Antagonists, Non-Sedating
  • Piperidines
  • Polyunsaturated Alkamides
  • Terfenadine
  • fexofenadine
  • piperine