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A multi-center prec...
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Karageorgis, AnastassiaAstraZeneca AB,Safety and ADME Translational Sciences, Drug Safety and Metabolism, AstraZeneca, Gothenburg, Sweden.
(författare)
A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function
- Artikel/kapitelEngelska2018
Förlag, utgivningsår, omfång ...
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2018-05-17
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Public Library of Science (PLoS),2018
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electronicrdacarrier
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LIBRIS-ID:oai:research.chalmers.se:32f4a9c2-2030-4881-afc9-f5bf3d1c6cf3
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https://doi.org/10.1371/journal.pone.0197213DOI
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https://research.chalmers.se/publication/530627URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-148072URI
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Språk:engelska
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Sammanfattning på:engelska
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Funding agencies: HESI; National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA) [P00800]; National Institutes of Health from the National Institute of General Medical Sciences [R01 GM041935, R35 GM122576]
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Drug-induced liver injury (Dili) is a leading cause of acute liver failure and transplantation. Dili can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers. The mean gadoxetate uptake rate constant for the vehicle groups at all centers was 39.3 +/- 3.4 s -1 (n = 23) and 11.7 +/- 1.3 s -1 (n = 20) for the rifampicin groups. The mean gadoxetate efflux rate constant for the vehicle groups was 1.53 +/- 0.08 s -1 (n = 23) and for the rifampicin treated groups was 0.94 +/- 0.08 s -1 (n = 20). Both the uptake and excretion transporters of gadoxetate were statistically significantly inhibited by the clinical dose of rifampicin at all centers and the size of this treatment group effect was consistent across the centers. Gadoxetate is a clinically approved MRI contrast agent, so this method is readily transferable to the clinic. Conclusion: Rate constants of
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Lenhard, Stephen C.GlaxoSmithKline,Bioimaging, Platform Technology and Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America.
(författare)
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Yerby, BrittanyAmgen Incorporated,Research Imaging Sciences, Amgen, Thousand Oaks, California, United States of America.
(författare)
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Forsgren, MikaelLinköpings universitet,Avdelningen för radiologiska vetenskaper,Medicinska fakulteten,Centrum för medicinsk bildvetenskap och visualisering, CMIV,Wolfram MathCore, Linköping, Sweden(Swepub:liu)mikfo34
(författare)
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Liachenko, SergueiNational Center for Toxicological Research, Division of Neurotoxicology, United States Food and Drug Administration, Jefferson, Arkansas, United States of America.
(författare)
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Johansson, EdvinAstraZeneca AB,Personalised Healthcare and Biomarkers, Imaging group, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
(författare)
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Pilling, Mark A.AstraZeneca AB,Biostatistics, Quantitative Biology, Discovery Sciences, Innovative Medicines and Early Development, AstraZeneca RandD, Cambridge, United Kingdom.
(författare)
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Peterson, Richard A.GlaxoSmithKline,Safety Assessment, GlaxoSmithKline, Research Triangle Park, Durham, North Carolina, United States of America.
(författare)
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Yang, XiNational Center for Toxicological Research, Division of Systems Biology, United States Food and Drug Administration, Jefferson, Arkansas, United States of America.
(författare)
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Williams, Dominic P.AstraZeneca AB,Safety and ADME Translational Sciences, Drug Safety and Metabolism, AstraZeneca, Cambridge, United Kingdom.
(författare)
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Ungersma, Sharon E.Amgen Incorporated,Research Imaging Sciences, Amgen, Thousand Oaks, California, United States of America.
(författare)
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Morgan, Ryan E.Amgen Incorporated,Department of Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America.
(författare)
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Brouwer, Kim L.R.The University of North Carolina at Chapel Hill,Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of N orth Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
(författare)
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Jucker, Beat M.GlaxoSmithKline,Bioimaging, Platform Technology and Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America.
(författare)
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Hockings, Paul,1956Chalmers tekniska högskola,Chalmers University of Technology,Antaros Medical, BioVenture Hub, Mölndal, Sweden.; MedTech West, Chalmers University of Technology, Gothenburg, Sweden.(Swepub:cth)hockings
(författare)
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AstraZeneca ABSafety and ADME Translational Sciences, Drug Safety and Metabolism, AstraZeneca, Gothenburg, Sweden.
(creator_code:org_t)
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Ingår i:PLoS ONE: Public Library of Science (PLoS)13:51932-62031932-6203
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Karageorgis, Ana ...
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Lenhard, Stephen ...
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Yerby, Brittany
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Forsgren, Mikael
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Liachenko, Sergu ...
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Johansson, Edvin
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visa fler...
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Pilling, Mark A.
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Peterson, Richar ...
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Yang, Xi
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Williams, Domini ...
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Ungersma, Sharon ...
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Morgan, Ryan E.
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Brouwer, Kim L.R ...
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Jucker, Beat M.
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Hockings, Paul, ...
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