Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients

Abstract Although the use of excipients is widespread, a thorough understanding of the drug interaction potential of these compounds remains a frequent topic of current research. Not only can excipients alter the disposition of coformulated drugs, but it is likely that these effects on co‐administer...

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Autores principales:	Savannah J. McFeely, Jingjing Yu, Yan Wang, Cheryl Wu, Isabelle Ragueneau‐Majlessi
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/253be63d1edb4eceb745e2080720f664
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spelling	oai:doaj.org-article:253be63d1edb4eceb745e2080720f6642021-11-19T15:35:30ZExcipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients2163-830610.1002/psp4.12668https://doaj.org/article/253be63d1edb4eceb745e2080720f6642021-08-01T00:00:00Zhttps://doi.org/10.1002/psp4.12668https://doaj.org/toc/2163-8306Abstract Although the use of excipients is widespread, a thorough understanding of the drug interaction potential of these compounds remains a frequent topic of current research. Not only can excipients alter the disposition of coformulated drugs, but it is likely that these effects on co‐administered drugs can reach to clinical significance leading to potential adverse effects or loss of efficacy. These risks can be evaluated through use of in silico methods of mechanistic modeling, including approaches, such as population pharmacokinetic (PK) and physiologically‐based PK modeling, which require a comprehensive understanding of the compounds to ensure accurate predictions. We established a knowledgebase of the available compound (or substance) and interaction‐specific parameters with the goal of providing a single source of physiochemical, in vitro, and clinical PK and interaction data of commonly used excipients. To illustrate the utility of this knowledgebase, a model for cremophor EL was developed and used to hypothesize the potential for CYP3A‐ and P‐gp‐based interactions as a proof of concept.Savannah J. McFeelyJingjing YuYan WangCheryl WuIsabelle Ragueneau‐MajlessiWileyarticleTherapeutics. PharmacologyRM1-950ENCPT: Pharmacometrics & Systems Pharmacology, Vol 10, Iss 8, Pp 953-961 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Savannah J. McFeely Jingjing Yu Yan Wang Cheryl Wu Isabelle Ragueneau‐Majlessi Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients
description	Abstract Although the use of excipients is widespread, a thorough understanding of the drug interaction potential of these compounds remains a frequent topic of current research. Not only can excipients alter the disposition of coformulated drugs, but it is likely that these effects on co‐administered drugs can reach to clinical significance leading to potential adverse effects or loss of efficacy. These risks can be evaluated through use of in silico methods of mechanistic modeling, including approaches, such as population pharmacokinetic (PK) and physiologically‐based PK modeling, which require a comprehensive understanding of the compounds to ensure accurate predictions. We established a knowledgebase of the available compound (or substance) and interaction‐specific parameters with the goal of providing a single source of physiochemical, in vitro, and clinical PK and interaction data of commonly used excipients. To illustrate the utility of this knowledgebase, a model for cremophor EL was developed and used to hypothesize the potential for CYP3A‐ and P‐gp‐based interactions as a proof of concept.
format	article
author	Savannah J. McFeely Jingjing Yu Yan Wang Cheryl Wu Isabelle Ragueneau‐Majlessi
author_facet	Savannah J. McFeely Jingjing Yu Yan Wang Cheryl Wu Isabelle Ragueneau‐Majlessi
author_sort	Savannah J. McFeely
title	Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients
title_short	Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients
title_full	Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients
title_fullStr	Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients
title_full_unstemmed	Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients
title_sort	excipient knowledgebase: development of a comprehensive tool for understanding the disposition and interaction potential of common excipients
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/253be63d1edb4eceb745e2080720f664
work_keys_str_mv	AT savannahjmcfeely excipientknowledgebasedevelopmentofacomprehensivetoolforunderstandingthedispositionandinteractionpotentialofcommonexcipients AT jingjingyu excipientknowledgebasedevelopmentofacomprehensivetoolforunderstandingthedispositionandinteractionpotentialofcommonexcipients AT yanwang excipientknowledgebasedevelopmentofacomprehensivetoolforunderstandingthedispositionandinteractionpotentialofcommonexcipients AT cherylwu excipientknowledgebasedevelopmentofacomprehensivetoolforunderstandingthedispositionandinteractionpotentialofcommonexcipients AT isabelleragueneaumajlessi excipientknowledgebasedevelopmentofacomprehensivetoolforunderstandingthedispositionandinteractionpotentialofcommonexcipients
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Excipient knowledgebase: Development of a comprehensive tool for understanding the disposition and interaction potential of common excipients

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