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Sökning: WFRF:(Brouwer Kim L.R.) > A multi-center prec...

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FältnamnIndikatorerMetadata
00006861naa a2200589 4500
001oai:research.chalmers.se:32f4a9c2-2030-4881-afc9-f5bf3d1c6cf3
003SwePub
008220601s2018 | |||||||||||000 ||eng|
009oai:DiVA.org:liu-148072
0247 a https://doi.org/10.1371/journal.pone.01972132 DOI
0247 a https://research.chalmers.se/publication/5306272 URI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1480722 URI
040 a (SwePub)cthd (SwePub)liu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Karageorgis, Anastassiau AstraZeneca AB,Safety and ADME Translational Sciences, Drug Safety and Metabolism, AstraZeneca, Gothenburg, Sweden.4 aut
2451 0a A multi-center preclinical study of gadoxetate DCE-MRI in rats as a biomarker of drug induced inhibition of liver transporter function
264 c 2018-05-17
264 1b Public Library of Science (PLoS),c 2018
338 a electronic2 rdacarrier
500 a 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]
520 a 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
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmakologi och toxikologi0 (SwePub)301022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmacology and Toxicology0 (SwePub)301022 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Radiologi och bildbehandling0 (SwePub)302082 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Radiology, Nuclear Medicine and Medical Imaging0 (SwePub)302082 hsv//eng
7001 a Lenhard, Stephen C.u GlaxoSmithKline,Bioimaging, Platform Technology and Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America.4 aut
7001 a Yerby, Brittanyu Amgen Incorporated,Research Imaging Sciences, Amgen, Thousand Oaks, California, United States of America.4 aut
7001 a Forsgren, Mikaelu Linköpings universitet,Avdelningen för radiologiska vetenskaper,Medicinska fakulteten,Centrum för medicinsk bildvetenskap och visualisering, CMIV,Wolfram MathCore, Linköping, Sweden4 aut0 (Swepub:liu)mikfo34
7001 a Liachenko, Sergueiu National Center for Toxicological Research, Division of Neurotoxicology, United States Food and Drug Administration, Jefferson, Arkansas, United States of America.4 aut
7001 a Johansson, Edvinu AstraZeneca AB,Personalised Healthcare and Biomarkers, Imaging group, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.4 aut
7001 a Pilling, Mark A.u AstraZeneca AB,Biostatistics, Quantitative Biology, Discovery Sciences, Innovative Medicines and Early Development, AstraZeneca RandD, Cambridge, United Kingdom.4 aut
7001 a Peterson, Richard A.u GlaxoSmithKline,Safety Assessment, GlaxoSmithKline, Research Triangle Park, Durham, North Carolina, United States of America.4 aut
7001 a Yang, Xiu National Center for Toxicological Research, Division of Systems Biology, United States Food and Drug Administration, Jefferson, Arkansas, United States of America.4 aut
7001 a Williams, Dominic P.u AstraZeneca AB,Safety and ADME Translational Sciences, Drug Safety and Metabolism, AstraZeneca, Cambridge, United Kingdom.4 aut
7001 a Ungersma, Sharon E.u Amgen Incorporated,Research Imaging Sciences, Amgen, Thousand Oaks, California, United States of America.4 aut
7001 a Morgan, Ryan E.u Amgen Incorporated,Department of Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, California, United States of America.4 aut
7001 a Brouwer, Kim L.R.u 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.4 aut
7001 a Jucker, Beat M.u GlaxoSmithKline,Bioimaging, Platform Technology and Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America.4 aut
7001 a Hockings, Paul,d 1956u Chalmers tekniska högskola,Chalmers University of Technology,Antaros Medical, BioVenture Hub, Mölndal, Sweden.; MedTech West, Chalmers University of Technology, Gothenburg, Sweden.4 aut0 (Swepub:cth)hockings
7102 a AstraZeneca ABb Safety and ADME Translational Sciences, Drug Safety and Metabolism, AstraZeneca, Gothenburg, Sweden.4 org
7730 t PLoS ONEd : Public Library of Science (PLoS)g 13:5q 13:5x 1932-6203x 1932-6203
8564 u https://research.chalmers.se/publication/530627/file/530627_Fulltext.pdfx primaryx freey FULLTEXT
8564 u https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0197213&type=printable
8564 u https://liu.diva-portal.org/smash/get/diva2:1210963/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://doi.org/10.1371/journal.pone.0197213
8564 8u https://research.chalmers.se/publication/530627
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-148072

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