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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.

4 Issues per year

CiteScore 2017: 1.46

SCImago Journal Rank (SJR) 2017: 0.531
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Volume 31, Issue 4


Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition

Bhargavi Latha Athukuri
  • DMPK and Clinical Pharmacology Division, Department of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506 009, T.S. India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Prasad Neerati
  • Corresponding author
  • DMPK and Clinical Pharmacology Division, Department of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506 009, T.S. India
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  • Other articles by this author:
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Published Online: 2016-11-22 | DOI: https://doi.org/10.1515/dmpt-2016-0029



Cytochrome P450-2D6 (CYP2D6), a member of the CYP450 mixed function oxidase system, is an important CYP isoform with regard to herbal-drug interactions and is responsible for the metabolism of nearly 25% of drugs. Until now, studies on the effects of various phytochemicals on CYP2D6 activity in vivo have been very rare. Gallic acid and ellagic acid are natural polyphenols which are widely distributed in fruits and medicinal plants. In the present study, the effects of gallic acid and ellagic acid pretreatment on intestinal transport and oral bioavailability of metoprolol were investigated.


The intestinal transport of metoprolol was assessed by conducting an in situ single pass intestinal perfusion (SPIP) study. The bioavailability study was conducted to evaluate the pharmacokinetic parameters of orally administered metoprolol in rats.


After pretreatment with gallic acid and ellagic acid, no significant change in effective permeability of metoprolol was observed at the ileum part of rat intestine. A significant improvement in the peak plasma concentration (Cmax) and area under the serum concentration–time profile (AUC) and decrease in clearance were observed in rats pretreated with gallic acid and ellagic acid.


Gallic acid and ellagic acid significantly enhanced the oral bioavailability of metoprolol by inhibiting CYP2D6-mediated metabolism in the rat liver. Hence, adverse herbal-drug interactions may result with concomitant ingestion of gallic acid and ellagic acid supplements and drugs that are CYP2D6 substrates. The clinical assessment of these interactions should be further investigated in human volunteers.

Keywords: cytochrome P450; ellagic acid; gallic acid; metoprolol; quinidine


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About the article

Received: 2016-09-09

Accepted: 2016-11-01

Published Online: 2016-11-22

Published in Print: 2016-12-01

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Drug Metabolism and Personalized Therapy, Volume 31, Issue 4, Pages 229–234, ISSN (Online) 2363-8915, ISSN (Print) 2363-8907, DOI: https://doi.org/10.1515/dmpt-2016-0029.

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