Enteric reabsorption processes and their impact on drug pharmacokinetics

Abstract Enteric reabsorption occurs when a drug is secreted into the intestinal lumen and reabsorbed into the systemic circulation. This distribution process is evidenced by multiple peaks in pharmacokinetic profiles. Commonly, hepatobiliary drug secretion is assumed to be the underlying mechanism...

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Autores principales:	Manuel Ibarra, Iñaki F. Trocóniz, Pietro Fagiolino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06f6fe54abf34410957ca74df2962c43
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spelling	oai:doaj.org-article:06f6fe54abf34410957ca74df2962c432021-12-02T13:30:51ZEnteric reabsorption processes and their impact on drug pharmacokinetics10.1038/s41598-021-85174-w2045-2322https://doaj.org/article/06f6fe54abf34410957ca74df2962c432021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85174-whttps://doaj.org/toc/2045-2322Abstract Enteric reabsorption occurs when a drug is secreted into the intestinal lumen and reabsorbed into the systemic circulation. This distribution process is evidenced by multiple peaks in pharmacokinetic profiles. Commonly, hepatobiliary drug secretion is assumed to be the underlying mechanism (enterohepatic reabsorption, EHR), neglecting other possible mechanisms such as gastric secretion (enterogastric reabsorption, EGR). In addition, the impact of drug reabsorption on systemic clearance, volume of distribution and bioavailability has been a subject of long-standing discussions. In this work, we propose semi-mechanistic pharmacokinetic models to reflect EHR and EGR and compare their respective impact on primary pharmacokinetic parameters. A simulation-based analysis was carried out considering three drug types with the potential for reabsorption, classified according to their primary route of elimination and their hepatic extraction: (A) hepatic metabolism—low extraction; (B) hepatic metabolism—intermediate/high extraction; (C) renal excretion. Results show that an increase in EHR can significantly reduce the clearance of drugs A and B, increase bioavailability of B drugs, and increase the volume of distribution for all drugs. Conversely, EGR had negligible impact in all pharmacokinetic parameters. Findings provide background to explain and forecast the role that this process can play in pharmacokinetic variability, including drug-drug interactions and disease states.Manuel IbarraIñaki F. TrocónizPietro FagiolinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manuel Ibarra Iñaki F. Trocóniz Pietro Fagiolino Enteric reabsorption processes and their impact on drug pharmacokinetics
description	Abstract Enteric reabsorption occurs when a drug is secreted into the intestinal lumen and reabsorbed into the systemic circulation. This distribution process is evidenced by multiple peaks in pharmacokinetic profiles. Commonly, hepatobiliary drug secretion is assumed to be the underlying mechanism (enterohepatic reabsorption, EHR), neglecting other possible mechanisms such as gastric secretion (enterogastric reabsorption, EGR). In addition, the impact of drug reabsorption on systemic clearance, volume of distribution and bioavailability has been a subject of long-standing discussions. In this work, we propose semi-mechanistic pharmacokinetic models to reflect EHR and EGR and compare their respective impact on primary pharmacokinetic parameters. A simulation-based analysis was carried out considering three drug types with the potential for reabsorption, classified according to their primary route of elimination and their hepatic extraction: (A) hepatic metabolism—low extraction; (B) hepatic metabolism—intermediate/high extraction; (C) renal excretion. Results show that an increase in EHR can significantly reduce the clearance of drugs A and B, increase bioavailability of B drugs, and increase the volume of distribution for all drugs. Conversely, EGR had negligible impact in all pharmacokinetic parameters. Findings provide background to explain and forecast the role that this process can play in pharmacokinetic variability, including drug-drug interactions and disease states.
format	article
author	Manuel Ibarra Iñaki F. Trocóniz Pietro Fagiolino
author_facet	Manuel Ibarra Iñaki F. Trocóniz Pietro Fagiolino
author_sort	Manuel Ibarra
title	Enteric reabsorption processes and their impact on drug pharmacokinetics
title_short	Enteric reabsorption processes and their impact on drug pharmacokinetics
title_full	Enteric reabsorption processes and their impact on drug pharmacokinetics
title_fullStr	Enteric reabsorption processes and their impact on drug pharmacokinetics
title_full_unstemmed	Enteric reabsorption processes and their impact on drug pharmacokinetics
title_sort	enteric reabsorption processes and their impact on drug pharmacokinetics
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/06f6fe54abf34410957ca74df2962c43
work_keys_str_mv	AT manuelibarra entericreabsorptionprocessesandtheirimpactondrugpharmacokinetics AT inakiftroconiz entericreabsorptionprocessesandtheirimpactondrugpharmacokinetics AT pietrofagiolino entericreabsorptionprocessesandtheirimpactondrugpharmacokinetics
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Enteric reabsorption processes and their impact on drug pharmacokinetics

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