Establishing a systematic framework to characterise in vitro methods for human hepatic metabolic clearance |
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Author: | Gouliarmou, Varvara1; Lostia, Alfonso Maria1; Coecke, Sandra1; |
Organizations: |
1European Commission, Joint Research Centre (JRC), Via Enrico Fermi 2749, 21027 Ispra, VA, Italy 2Present address: VITO (Flemish Institute of Technological Research), Mol, Belgium 3European Food Safety Authority, Via Carlo Magno, 1A, 43126 Parma, PR, Italy
4US National Toxicology Program, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
5Istituto Superiore di Sanità, Environment & Health Dept., Viale Regina Elena 299, 00161 Rome, Italy 6Institute for Clinical Pharmacology and Toxicology, Charité, Universitätsmedizin Berlin, Charitéplatz 1, D-110117 Berlin, Germany 7Manchester Pharmacy School, University of Manchester, Manchester M13 9PT, UK 8Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium 9Computational Toxicology Laboratory, Exposure and Biomonitoring Division, Health Canada - Environmental Health Science and Research Bureau, 50 Colombine Dwy, Environmental Health Centre, Tunney's Pasture AL:0800C, Ottawa, ON K1A 0K9, Canada 10Research Unit of Biomedicine/Pharmacology and Toxicology, Faculty of Medicine, Aapistie 5 B, FIN-90014, University of Oulu, Finland 11U.S. EPA, Office of Research and Development, National Exposure Research Laboratory, 109 T.W. Alexander Drive, MD E243-04, Research Triangle Park, NC 27711, USA 12Discovery DMPK, Merck KGaA Darmstadt, Germany |
Format: | article |
Version: | accepted version |
Access: | open |
Online Access: | PDF Full Text (PDF, 1.2 MB) |
Persistent link: | http://urn.fi/urn:nbn:fi-fe2019042413184 |
Language: | English |
Published: |
Elsevier,
2018
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Publish Date: | 2019-08-09 |
Description: |
AbstractHepatic metabolic clearance is one of the most important factors driving the overall kinetics of chemicals including substances used in various product categories such as pesticides, biocides, pharmaceuticals, and cosmetics. A large number of in vitro systems from purified isozymes and subcellular organelles to hepatocytes in simple cultures and in complex scaffold setups are available for measuring hepatic metabolic clearance for different applications. However, there is currently no approach for systematically characterising and comparing these in vitro methods in terms of their design, applicability and performance. To address this, existing knowledge in the field of in vitro human hepatic metabolic clearance methods was gathered and analysed in order to establish a framework to systematically characterise methods based on a set of relevant components. An analogous framework would be also applicable for non-human in vitro systems. The components are associated with the biological test systems used (e.g. subcellular or cells), the in vitro method (e.g. number of cells, test item solubility), related analytical techniques, data interpretation methods (based on substrate depletion/metabolite formation), and performance assessments (precision and accuracy of clearance measurements). To facilitate the regulatory acceptance of this class of methods, it is intended that the framework provide the basis of harmonisation work within the OECD. see all
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Series: |
Toxicology in vitro |
ISSN: | 0887-2333 |
ISSN-E: | 1879-3177 |
ISSN-L: | 0887-2333 |
Volume: | 53 |
Pages: | 233 - 244 |
DOI: | 10.1016/j.tiv.2018.08.004 |
OADOI: | https://oadoi.org/10.1016/j.tiv.2018.08.004 |
Type of Publication: |
A1 Journal article – refereed |
Field of Science: |
317 Pharmacy |
Subjects: | |
Copyright information: |
© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
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https://creativecommons.org/licenses/by-nc-nd/4.0/ |