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Quantitative predic...
Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips
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- Herland, Anna (author)
- Karolinska Institutet,KTH,Mikro- och nanosystemteknik
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Maoz, B. M. (author)
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Das, D. (author)
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Somayaji, M. R. (author)
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Prantil-Baun, R. (author)
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Novak, R. (author)
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Cronce, M. (author)
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Huffstater, T. (author)
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Jeanty, S. S. F. (author)
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Ingram, M. (author)
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Chalkiadaki, A. (author)
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Benson Chou, D. (author)
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Marquez, S. (author)
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Delahanty, A. (author)
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Jalili-Firoozinezhad, S. (author)
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Milton, Y. (author)
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Sontheimer-Phelps, A. (author)
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Swenor, B. (author)
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Levy, O. (author)
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Parker, K. K. (author)
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Przekwas, A. (author)
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- Ingber, Donald (author)
- KTH,Mikro- och nanosystemteknik
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(creator_code:org_t)
- 2020-01-27
- 2020
- English.
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In: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 4:4, s. 421-436
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https://www.ncbi.nlm...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- 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.
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Nanoteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Nano-technology (hsv//eng)
Keyword
- Forecasting
- Hospital data processing
- Metabolism
- Pharmacokinetics
- Clinical trial
- Drug absorption
- Drug administration
- Human pharmacokinetics
- Liquid transfers
- Patient data
- PD parameters
- Quantitative prediction
- Physiological models
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Herland, Anna
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Maoz, B. M.
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Das, D.
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Somayaji, M. R.
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Prantil-Baun, R.
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Novak, R.
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show more...
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Cronce, M.
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Huffstater, T.
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Jeanty, S. S. F.
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Ingram, M.
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Chalkiadaki, A.
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Benson Chou, D.
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Marquez, S.
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Delahanty, A.
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Jalili-Firoozine ...
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Milton, Y.
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Sontheimer-Phelp ...
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Swenor, B.
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Levy, O.
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Parker, K. K.
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Przekwas, A.
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Ingber, Donald
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show less...
- About the subject
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Nano technology
- Articles in the publication
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Nature Biomedica ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet