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Potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: A Pharmacokinetic Experiment

Background: Presently, varied case reports demonstrated an increase or decrease in blood concentration of diverse conventional drugs, often co-administered with edible fruits, spices, or vegetables. The overarching aim of this research is to elucidate the fluctuations in tacrolimus (TAC) blood conce...

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Autores principales: Karwasra, Ritu, Ahmad, Sayeed, Singh, Surender
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154516/
https://www.ncbi.nlm.nih.gov/pubmed/37153790
http://dx.doi.org/10.3389/fphar.2023.1140706
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author Karwasra, Ritu
Ahmad, Sayeed
Singh, Surender
author_facet Karwasra, Ritu
Ahmad, Sayeed
Singh, Surender
author_sort Karwasra, Ritu
collection PubMed
description Background: Presently, varied case reports demonstrated an increase or decrease in blood concentration of diverse conventional drugs, often co-administered with edible fruits, spices, or vegetables. The overarching aim of this research is to elucidate the fluctuations in tacrolimus (TAC) blood concentration on the consumption of pomegranate rind extract (PRE). Methods: A pharmacokinetic (PK) study was conducted with two groups, vis-a-vis PRE + TAC (3 mg/kg) and TAC (3 mg/kg) alone groups. An experimental study was conducted in three different manners: Single-dose (S) PRE (200 mg/kg), 7-day repetitive (7-R) PRE (200 mg/kg) dosing, and multiple (M) PRE doses (100, 200, 400, and 800 mg/kg). All the blood samples (approximately 300 μl) were drawn at different time intervals, i.e., 30 min, 1, 2, 4, 8, and 12 h after oral administration of TAC (3 mg/kg). The estimation of TAC in rat plasma was done using the hyphenated technique LC-MS/MS where the mass spectrometer used was a triple-stage quadrupole in multiple-reaction monitoring (MRM) mode. Results: The findings depict that in comparison with the TAC (3 mg/kg) alone group with the 7-day repetitive (7-R) PRE (200 mg/kg) dosing, the Cmax was found to be 9.03 ± 1.21 ng/ml; AUC from time zero to infinity (AUC0-∞), 61.91 ± 17.37 ngh/ml, while the TAC (3 mg/kg) + PRE group exhibited an increase in PK parameters of TAC (Cmax 22.48 ± 3.07 ng/ml; AUC0-∞ 153.08 ± 13.24 ng h/ml). The authors further investigated in what manner the PRE affects the PK of TAC in animals. For this, docking studies with major phytoconstituents present in the PRE with CYP3A4 isoenzyme were carried out. Ellagitannins (dock score, −11.64) and punicalagin (dock score, −10.68) were again used for molecular simulation studies with TAC. To validate our findings, a CYP3A4 inhibitory in vitro assay was conducted. Conclusion: Based on the integrated in vivo and in silico studies, we concluded that pomegranate rind extract interacts strongly with CYP isoenzyme and is therefore responsible for the altered PK profile of TAC.
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spelling pubmed-101545162023-05-04 Potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: A Pharmacokinetic Experiment Karwasra, Ritu Ahmad, Sayeed Singh, Surender Front Pharmacol Pharmacology Background: Presently, varied case reports demonstrated an increase or decrease in blood concentration of diverse conventional drugs, often co-administered with edible fruits, spices, or vegetables. The overarching aim of this research is to elucidate the fluctuations in tacrolimus (TAC) blood concentration on the consumption of pomegranate rind extract (PRE). Methods: A pharmacokinetic (PK) study was conducted with two groups, vis-a-vis PRE + TAC (3 mg/kg) and TAC (3 mg/kg) alone groups. An experimental study was conducted in three different manners: Single-dose (S) PRE (200 mg/kg), 7-day repetitive (7-R) PRE (200 mg/kg) dosing, and multiple (M) PRE doses (100, 200, 400, and 800 mg/kg). All the blood samples (approximately 300 μl) were drawn at different time intervals, i.e., 30 min, 1, 2, 4, 8, and 12 h after oral administration of TAC (3 mg/kg). The estimation of TAC in rat plasma was done using the hyphenated technique LC-MS/MS where the mass spectrometer used was a triple-stage quadrupole in multiple-reaction monitoring (MRM) mode. Results: The findings depict that in comparison with the TAC (3 mg/kg) alone group with the 7-day repetitive (7-R) PRE (200 mg/kg) dosing, the Cmax was found to be 9.03 ± 1.21 ng/ml; AUC from time zero to infinity (AUC0-∞), 61.91 ± 17.37 ngh/ml, while the TAC (3 mg/kg) + PRE group exhibited an increase in PK parameters of TAC (Cmax 22.48 ± 3.07 ng/ml; AUC0-∞ 153.08 ± 13.24 ng h/ml). The authors further investigated in what manner the PRE affects the PK of TAC in animals. For this, docking studies with major phytoconstituents present in the PRE with CYP3A4 isoenzyme were carried out. Ellagitannins (dock score, −11.64) and punicalagin (dock score, −10.68) were again used for molecular simulation studies with TAC. To validate our findings, a CYP3A4 inhibitory in vitro assay was conducted. Conclusion: Based on the integrated in vivo and in silico studies, we concluded that pomegranate rind extract interacts strongly with CYP isoenzyme and is therefore responsible for the altered PK profile of TAC. Frontiers Media S.A. 2023-04-19 /pmc/articles/PMC10154516/ /pubmed/37153790 http://dx.doi.org/10.3389/fphar.2023.1140706 Text en Copyright © 2023 Karwasra, Ahmad and Singh. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Karwasra, Ritu
Ahmad, Sayeed
Singh, Surender
Potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: A Pharmacokinetic Experiment
title Potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: A Pharmacokinetic Experiment
title_full Potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: A Pharmacokinetic Experiment
title_fullStr Potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: A Pharmacokinetic Experiment
title_full_unstemmed Potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: A Pharmacokinetic Experiment
title_short Potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: A Pharmacokinetic Experiment
title_sort potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: a pharmacokinetic experiment
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154516/
https://www.ncbi.nlm.nih.gov/pubmed/37153790
http://dx.doi.org/10.3389/fphar.2023.1140706
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