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Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature

Background: Available in-vitro and animal studies indicate that inflammation impacts cytochromes P450 (CYP) activity via multiple and complex transcriptional and post-transcriptional mechanisms, depending on the specific CYP isoforms and the nature of inflammation mediators. It is essential to revie...

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Autores principales: Lenoir, Camille, Rollason, Victoria, Desmeules, Jules A., Samer, Caroline F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637893/
https://www.ncbi.nlm.nih.gov/pubmed/34867341
http://dx.doi.org/10.3389/fphar.2021.733935
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author Lenoir, Camille
Rollason, Victoria
Desmeules, Jules A.
Samer, Caroline F.
author_facet Lenoir, Camille
Rollason, Victoria
Desmeules, Jules A.
Samer, Caroline F.
author_sort Lenoir, Camille
collection PubMed
description Background: Available in-vitro and animal studies indicate that inflammation impacts cytochromes P450 (CYP) activity via multiple and complex transcriptional and post-transcriptional mechanisms, depending on the specific CYP isoforms and the nature of inflammation mediators. It is essential to review the current published data on the impact of inflammation on CYP activities in adults to support drug individualization based on comorbidities and diseases in clinical practice. Methods: This systematic review was conducted in PubMed through 7th January 2021 looking for articles that investigated the consequences of inflammation on CYP activities in adults. Information on the source of inflammation, victim drugs (and CYPs involved), effect of disease-drug interaction, number of subjects, and study design were extracted. Results: The search strategy identified 218 studies and case reports that met our inclusion criteria. These articles were divided into fourteen different sources of inflammation (such as infection, autoimmune diseases, cancer, therapies with immunomodulator…). The impact of inflammation on CYP activities appeared to be isoform-specific and dependent on the nature and severity of the underlying disease causing the inflammation. Some of these drug-disease interactions had a significant influence on drug pharmacokinetic parameters and on clinical management. For example, clozapine levels doubled with signs of toxicity during infections and the concentration ratio between clopidogrel’s active metabolite and clopidogrel is 48-fold lower in critically ill patients. Infection and CYP3A were the most cited perpetrator of inflammation and the most studied CYP, respectively. Moreover, some data suggest that resolution of inflammation results in a return to baseline CYP activities. Conclusion: Convincing evidence shows that inflammation is a major factor to be taken into account in drug development and in clinical practice to avoid any efficacy or safety issues because inflammation modulates CYP activities and thus drug pharmacokinetics. The impact is different depending on the CYP isoform and the inflammatory disease considered. Moreover, resolution of inflammation appears to result in a normalization of CYP activity. However, some results are still equivocal and further investigations are thus needed.
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spelling pubmed-86378932021-12-03 Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature Lenoir, Camille Rollason, Victoria Desmeules, Jules A. Samer, Caroline F. Front Pharmacol Pharmacology Background: Available in-vitro and animal studies indicate that inflammation impacts cytochromes P450 (CYP) activity via multiple and complex transcriptional and post-transcriptional mechanisms, depending on the specific CYP isoforms and the nature of inflammation mediators. It is essential to review the current published data on the impact of inflammation on CYP activities in adults to support drug individualization based on comorbidities and diseases in clinical practice. Methods: This systematic review was conducted in PubMed through 7th January 2021 looking for articles that investigated the consequences of inflammation on CYP activities in adults. Information on the source of inflammation, victim drugs (and CYPs involved), effect of disease-drug interaction, number of subjects, and study design were extracted. Results: The search strategy identified 218 studies and case reports that met our inclusion criteria. These articles were divided into fourteen different sources of inflammation (such as infection, autoimmune diseases, cancer, therapies with immunomodulator…). The impact of inflammation on CYP activities appeared to be isoform-specific and dependent on the nature and severity of the underlying disease causing the inflammation. Some of these drug-disease interactions had a significant influence on drug pharmacokinetic parameters and on clinical management. For example, clozapine levels doubled with signs of toxicity during infections and the concentration ratio between clopidogrel’s active metabolite and clopidogrel is 48-fold lower in critically ill patients. Infection and CYP3A were the most cited perpetrator of inflammation and the most studied CYP, respectively. Moreover, some data suggest that resolution of inflammation results in a return to baseline CYP activities. Conclusion: Convincing evidence shows that inflammation is a major factor to be taken into account in drug development and in clinical practice to avoid any efficacy or safety issues because inflammation modulates CYP activities and thus drug pharmacokinetics. The impact is different depending on the CYP isoform and the inflammatory disease considered. Moreover, resolution of inflammation appears to result in a normalization of CYP activity. However, some results are still equivocal and further investigations are thus needed. Frontiers Media S.A. 2021-11-16 /pmc/articles/PMC8637893/ /pubmed/34867341 http://dx.doi.org/10.3389/fphar.2021.733935 Text en Copyright © 2021 Lenoir, Rollason, Desmeules and Samer. 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
Lenoir, Camille
Rollason, Victoria
Desmeules, Jules A.
Samer, Caroline F.
Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature
title Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature
title_full Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature
title_fullStr Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature
title_full_unstemmed Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature
title_short Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature
title_sort influence of inflammation on cytochromes p450 activity in adults: a systematic review of the literature
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637893/
https://www.ncbi.nlm.nih.gov/pubmed/34867341
http://dx.doi.org/10.3389/fphar.2021.733935
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