Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips.
Journal
Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
22
05
2019
accepted:
25
11
2019
pubmed:
29
1
2020
medline:
12
5
2020
entrez:
29
1
2020
Statut:
ppublish
Résumé
Analyses of drug pharmacokinetics (PKs) and pharmacodynamics (PDs) performed in animals are often not predictive of drug PKs and PDs in humans, and in vitro PK and PD modelling does not provide quantitative PK parameters. Here, we show that physiological PK modelling of first-pass drug absorption, metabolism and excretion in humans-using computationally scaled data from multiple fluidically linked two-channel organ chips-predicts PK parameters for orally administered nicotine (using gut, liver and kidney chips) and for intravenously injected cisplatin (using coupled bone marrow, liver and kidney chips). The chips are linked through sequential robotic liquid transfers of a common blood substitute by their endothelium-lined channels (as reported by Novak et al. in an associated Article) and share an arteriovenous fluid-mixing reservoir. We also show that predictions of cisplatin PDs match previously reported patient data. The quantitative in-vitro-to-in-vivo translation of PK and PD parameters and the prediction of drug absorption, distribution, metabolism, excretion and toxicity through fluidically coupled organ chips may improve the design of drug-administration regimens for phase-I clinical trials.
Identifiants
pubmed: 31988459
doi: 10.1038/s41551-019-0498-9
pii: 10.1038/s41551-019-0498-9
pmc: PMC8011576
mid: NIHMS1682549
doi:
Substances chimiques
Pharmaceutical Preparations
0
Nicotine
6M3C89ZY6R
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
421-436Subventions
Organisme : FDA HHS
ID : HHSF223201310079C
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009216
Pays : United States
Commentaires et corrections
Type : CommentIn
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