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

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgements

Satish Kumar Bedada acknowledges the University Grants Commission (UGC), New Delhi, India for financial support to carry out this research work.

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Authors and Affiliations

  1. Drug Metabolism and Pharmacokinetics Division, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506009, Telangana State, India

    Satish Kumar Bedada & Praveen Kumar Boga

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  1. Satish Kumar Bedada
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  2. Praveen Kumar Boga
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Correspondence to Satish Kumar Bedada.

Ethics declarations

The protocol was approved by an institutional human ethical committee and was conducted in compliance with the ethical principles from the Declaration of Helsinki and with all International Conference on Harmonisation Good Clinical Practice Guidelines. Informed consent was obtained from all the volunteers included in the study.

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The authors declare that there are no conflicts of interest.

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Bedada, S.K., Boga, P.K. The influence of piperine on the pharmacokinetics of fexofenadine, a P-glycoprotein substrate, in healthy volunteers. Eur J Clin Pharmacol 73, 343–349 (2017). https://doi.org/10.1007/s00228-016-2173-3

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  • DOI: https://doi.org/10.1007/s00228-016-2173-3

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