Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective. Kenna, J. G., Taskar, K. S., Battista, C., Bourdet, D. L., Brouwer, K. L., Brouwer, K. R., Dai, D., Funk, C., Hafey, M. J., Lai, Y., Maher, J., Pak, Y. A., Pedersen, J. M., Polli, J. W., Rodrigues, A. D., Watkins, P. B., Yang, K., & Yucha, R. W. Clinical Pharmacology and Therapeutics, 104(5):916–932, November, 2018. ![Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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 (Css,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.
@article{kenna_can_2018,
title = {Can {Bile} {Salt} {Export} {Pump} {Inhibition} {Testing} in {Drug} {Discovery} and {Development} {Reduce} {Liver} {Injury} {Risk}? {An} {International} {Transporter} {Consortium} {Perspective}},
volume = {104},
issn = {0009-9236},
shorttitle = {Can {Bile} {Salt} {Export} {Pump} {Inhibition} {Testing} in {Drug} {Discovery} and {Development} {Reduce} {Liver} {Injury} {Risk}?},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220754/},
doi = {10.1002/cpt.1222},
abstract = {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 (Css,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.},
number = {5},
urldate = {2018-12-04},
journal = {Clinical Pharmacology and Therapeutics},
author = {Kenna, J. Gerry and Taskar, Kunal S. and Battista, Christina and Bourdet, David L. and Brouwer, Kim L.R. and Brouwer, Kenneth R. and Dai, David and Funk, Christoph and Hafey, Michael J. and Lai, Yurong and Maher, Jonathan and Pak, Y. Anne and Pedersen, Jenny M. and Polli, Joseph W. and Rodrigues, A. David and Watkins, Paul B. and Yang, Kyunghee and Yucha, Robert W.},
month = nov,
year = {2018},
pmid = {30137645},
pmcid = {PMC6220754},
pages = {916--932},
}
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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 (Css,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 \nBSEP inhibition data and may be undertaken on a case‐by‐case basis. 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