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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Camille Lenoir, Victoria Rollason, Jules A. Desmeules, Caroline F. Samer
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	inflammation cytochrome P450 pharmacokinetic disease-drug interaction cytokines Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5ffe811d918f48c8af530e24354d6afd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5ffe811d918f48c8af530e24354d6afd
record_format	dspace
spelling	oai:doaj.org-article:5ffe811d918f48c8af530e24354d6afd2021-11-16T13:46:15ZInfluence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature1663-981210.3389/fphar.2021.733935https://doaj.org/article/5ffe811d918f48c8af530e24354d6afd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.733935/fullhttps://doaj.org/toc/1663-9812Background: 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.Camille LenoirCamille LenoirVictoria RollasonVictoria RollasonJules A. DesmeulesJules A. DesmeulesJules A. DesmeulesCaroline F. SamerCaroline F. SamerFrontiers Media S.A.articleinflammationcytochrome P450pharmacokineticdisease-drug interactioncytokinesTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	inflammation cytochrome P450 pharmacokinetic disease-drug interaction cytokines Therapeutics. Pharmacology RM1-950
spellingShingle	inflammation cytochrome P450 pharmacokinetic disease-drug interaction cytokines Therapeutics. Pharmacology RM1-950 Camille Lenoir Camille Lenoir Victoria Rollason Victoria Rollason Jules A. Desmeules Jules A. Desmeules Jules A. Desmeules Caroline F. Samer Caroline F. Samer Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature
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.
format	article
author	Camille Lenoir Camille Lenoir Victoria Rollason Victoria Rollason Jules A. Desmeules Jules A. Desmeules Jules A. Desmeules Caroline F. Samer Caroline F. Samer
author_facet	Camille Lenoir Camille Lenoir Victoria Rollason Victoria Rollason Jules A. Desmeules Jules A. Desmeules Jules A. Desmeules Caroline F. Samer Caroline F. Samer
author_sort	Camille Lenoir
title	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_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_sort	influence of inflammation on cytochromes p450 activity in adults: a systematic review of the literature
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5ffe811d918f48c8af530e24354d6afd
work_keys_str_mv	AT camillelenoir influenceofinflammationoncytochromesp450activityinadultsasystematicreviewoftheliterature AT camillelenoir influenceofinflammationoncytochromesp450activityinadultsasystematicreviewoftheliterature AT victoriarollason influenceofinflammationoncytochromesp450activityinadultsasystematicreviewoftheliterature AT victoriarollason influenceofinflammationoncytochromesp450activityinadultsasystematicreviewoftheliterature AT julesadesmeules influenceofinflammationoncytochromesp450activityinadultsasystematicreviewoftheliterature AT julesadesmeules influenceofinflammationoncytochromesp450activityinadultsasystematicreviewoftheliterature AT julesadesmeules influenceofinflammationoncytochromesp450activityinadultsasystematicreviewoftheliterature AT carolinefsamer influenceofinflammationoncytochromesp450activityinadultsasystematicreviewoftheliterature AT carolinefsamer influenceofinflammationoncytochromesp450activityinadultsasystematicreviewoftheliterature
_version_	1718426482450104320

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

Ejemplares similares