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Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective
Bile salt export pump (BSEP) inhibition has emerged as an important mechanism that may contribute to the initiation of human drug‐induced liver injury (DILI). Proactive evaluation and understanding of BSEP inhibition is recommended in drug discovery and development to aid internal decision making on...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220754/ https://www.ncbi.nlm.nih.gov/pubmed/30137645 http://dx.doi.org/10.1002/cpt.1222 |
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author | Kenna, J. Gerry Taskar, Kunal S. Battista, Christina Bourdet, David L. Brouwer, Kim L.R. Brouwer, Kenneth R. Dai, David Funk, Christoph Hafey, Michael J. Lai, Yurong Maher, Jonathan Pak, Y. Anne Pedersen, Jenny M. Polli, Joseph W. Rodrigues, A. David Watkins, Paul B. Yang, Kyunghee Yucha, Robert W. |
author_facet | Kenna, J. Gerry Taskar, Kunal S. Battista, Christina Bourdet, David L. Brouwer, Kim L.R. Brouwer, Kenneth R. Dai, David Funk, Christoph Hafey, Michael J. Lai, Yurong Maher, Jonathan Pak, Y. Anne Pedersen, Jenny M. Polli, Joseph W. Rodrigues, A. David Watkins, Paul B. Yang, Kyunghee Yucha, Robert W. |
author_sort | Kenna, J. Gerry |
collection | PubMed |
description | Bile salt export pump (BSEP) inhibition has emerged as an important mechanism that may contribute to the initiation of human drug‐induced liver injury (DILI). Proactive evaluation and understanding of BSEP inhibition is recommended in drug discovery and development to aid internal decision making on DILI risk. BSEP inhibition can be quantified using in vitro assays. When interpreting assay data, it is important to consider in vivo drug exposure. Currently, this can be undertaken most effectively by consideration of total plasma steady state drug concentrations (C(ss,plasma)). However, because total drug concentrations are not predictive of pharmacological effect, the relationship between total exposure and BSEP inhibition is not causal. Various follow‐up studies can aid interpretation of in vitro BSEP inhibition data and may be undertaken on a case‐by‐case basis. BSEP inhibition is one of several mechanisms by which drugs may cause DILI, therefore, it should be considered alongside other mechanisms when evaluating possible DILI risk. |
format | Online Article Text |
id | pubmed-6220754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62207542018-11-13 Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective Kenna, J. Gerry Taskar, Kunal S. Battista, Christina Bourdet, David L. Brouwer, Kim L.R. Brouwer, Kenneth R. Dai, David Funk, Christoph Hafey, Michael J. Lai, Yurong Maher, Jonathan Pak, Y. Anne Pedersen, Jenny M. Polli, Joseph W. Rodrigues, A. David Watkins, Paul B. Yang, Kyunghee Yucha, Robert W. Clin Pharmacol Ther Reviews Bile salt export pump (BSEP) inhibition has emerged as an important mechanism that may contribute to the initiation of human drug‐induced liver injury (DILI). Proactive evaluation and understanding of BSEP inhibition is recommended in drug discovery and development to aid internal decision making on DILI risk. BSEP inhibition can be quantified using in vitro assays. When interpreting assay data, it is important to consider in vivo drug exposure. Currently, this can be undertaken most effectively by consideration of total plasma steady state drug concentrations (C(ss,plasma)). However, because total drug concentrations are not predictive of pharmacological effect, the relationship between total exposure and BSEP inhibition is not causal. Various follow‐up studies can aid interpretation of in vitro BSEP inhibition data and may be undertaken on a case‐by‐case basis. BSEP inhibition is one of several mechanisms by which drugs may cause DILI, therefore, it should be considered alongside other mechanisms when evaluating possible DILI risk. John Wiley and Sons Inc. 2018-10-22 2018-11 /pmc/articles/PMC6220754/ /pubmed/30137645 http://dx.doi.org/10.1002/cpt.1222 Text en © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Reviews Kenna, J. Gerry Taskar, Kunal S. Battista, Christina Bourdet, David L. Brouwer, Kim L.R. Brouwer, Kenneth R. Dai, David Funk, Christoph Hafey, Michael J. Lai, Yurong Maher, Jonathan Pak, Y. Anne Pedersen, Jenny M. Polli, Joseph W. Rodrigues, A. David Watkins, Paul B. Yang, Kyunghee Yucha, Robert W. Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective |
title | Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective |
title_full | Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective |
title_fullStr | Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective |
title_full_unstemmed | Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective |
title_short | Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective |
title_sort | can bile salt export pump inhibition testing in drug discovery and development reduce liver injury risk? an international transporter consortium perspective |
topic | Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220754/ https://www.ncbi.nlm.nih.gov/pubmed/30137645 http://dx.doi.org/10.1002/cpt.1222 |
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