Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier

Efflux transport systems are essential to suppress the absorption of xenobiotics from the intestinal lumen and protect the critical tissues at the blood-tissue barriers, such as the blood–brain barrier. The function of drug efflux transport is dominated by various transporters. Accumulated clinical...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yoshiki Hashimoto, Kazuyoshi Michiba, Kazuya Maeda, Hiroyuki Kusuhara
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Efflux transporters Drug transport In vitro model cells Drug–drug interactions Pharmacokinetic models Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/52b58402967f4b5ea619d61a35dd957e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:52b58402967f4b5ea619d61a35dd957e
record_format	dspace
spelling	oai:doaj.org-article:52b58402967f4b5ea619d61a35dd957e2021-11-24T04:27:23ZQuantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier1347-861310.1016/j.jphs.2021.10.010https://doaj.org/article/52b58402967f4b5ea619d61a35dd957e2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1347861321001055https://doaj.org/toc/1347-8613Efflux transport systems are essential to suppress the absorption of xenobiotics from the intestinal lumen and protect the critical tissues at the blood-tissue barriers, such as the blood–brain barrier. The function of drug efflux transport is dominated by various transporters. Accumulated clinical evidences have revealed that genetic variations of the transporters, together with coadministered drugs, affect the expression and/or function of transporters and subsequently the pharmacokinetics of substrate drugs. Thus, in the preclinical stage of drug development, quantitative prediction of the impact of efflux transporters as well as that of uptake transporters and metabolic enzymes on the pharmacokinetics of drugs in humans has been performed using various in vitro experimental tools. Various kinds of human-derived cell systems can be applied to the precise prediction of drug transport in humans. Mathematical modeling consisting of each intrinsic metabolic or transport process enables us to understand the disposition of drugs both at the organ level and at the level of the whole body by integrating a variety of experimental results into model parameters. This review focuses on the role of efflux transporters in the intestinal absorption and brain distribution of drugs, in addition to recent advances in predictive tools and methodologies.Yoshiki HashimotoKazuyoshi MichibaKazuya MaedaHiroyuki KusuharaElsevierarticleEfflux transportersDrug transportIn vitro model cellsDrug–drug interactionsPharmacokinetic modelsTherapeutics. PharmacologyRM1-950ENJournal of Pharmacological Sciences, Vol 148, Iss 1, Pp 142-151 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Efflux transporters Drug transport In vitro model cells Drug–drug interactions Pharmacokinetic models Therapeutics. Pharmacology RM1-950
spellingShingle	Efflux transporters Drug transport In vitro model cells Drug–drug interactions Pharmacokinetic models Therapeutics. Pharmacology RM1-950 Yoshiki Hashimoto Kazuyoshi Michiba Kazuya Maeda Hiroyuki Kusuhara Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier
description	Efflux transport systems are essential to suppress the absorption of xenobiotics from the intestinal lumen and protect the critical tissues at the blood-tissue barriers, such as the blood–brain barrier. The function of drug efflux transport is dominated by various transporters. Accumulated clinical evidences have revealed that genetic variations of the transporters, together with coadministered drugs, affect the expression and/or function of transporters and subsequently the pharmacokinetics of substrate drugs. Thus, in the preclinical stage of drug development, quantitative prediction of the impact of efflux transporters as well as that of uptake transporters and metabolic enzymes on the pharmacokinetics of drugs in humans has been performed using various in vitro experimental tools. Various kinds of human-derived cell systems can be applied to the precise prediction of drug transport in humans. Mathematical modeling consisting of each intrinsic metabolic or transport process enables us to understand the disposition of drugs both at the organ level and at the level of the whole body by integrating a variety of experimental results into model parameters. This review focuses on the role of efflux transporters in the intestinal absorption and brain distribution of drugs, in addition to recent advances in predictive tools and methodologies.
format	article
author	Yoshiki Hashimoto Kazuyoshi Michiba Kazuya Maeda Hiroyuki Kusuhara
author_facet	Yoshiki Hashimoto Kazuyoshi Michiba Kazuya Maeda Hiroyuki Kusuhara
author_sort	Yoshiki Hashimoto
title	Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier
title_short	Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier
title_full	Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier
title_fullStr	Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier
title_full_unstemmed	Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier
title_sort	quantitative prediction of pharmacokinetic properties of drugs in humans: recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/52b58402967f4b5ea619d61a35dd957e
work_keys_str_mv	AT yoshikihashimoto quantitativepredictionofpharmacokineticpropertiesofdrugsinhumansrecentadvanceininvitromodelstopredicttheimpactofeffluxtransportersinthesmallintestineandbloodbrainbarrier AT kazuyoshimichiba quantitativepredictionofpharmacokineticpropertiesofdrugsinhumansrecentadvanceininvitromodelstopredicttheimpactofeffluxtransportersinthesmallintestineandbloodbrainbarrier AT kazuyamaeda quantitativepredictionofpharmacokineticpropertiesofdrugsinhumansrecentadvanceininvitromodelstopredicttheimpactofeffluxtransportersinthesmallintestineandbloodbrainbarrier AT hiroyukikusuhara quantitativepredictionofpharmacokineticpropertiesofdrugsinhumansrecentadvanceininvitromodelstopredicttheimpactofeffluxtransportersinthesmallintestineandbloodbrainbarrier
_version_	1718415975365214208

Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier

Ejemplares similares