{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:54:50Z","timestamp":1792101290177,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:p>\n                    To inform fetal drug safety, it is important to determine or predict fetal drug exposure throughout pregnancy. The former is not possible in the first or second trimester. In contrast, at the time of birth, fetal drug exposure, relative to maternal exposure, can be estimated as\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>p,uu<\/jats:sub>\n                    (unbound fetal umbilical venous (UV) plasma area under the curve (AUC)\/unbound maternal plasma (MP) AUC), provided the observed UV\/MP values, spanning the dosing interval, are available from multiple maternal\u2010fetal dyads. However, this fetal\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>p,uu<\/jats:sub>\n                    cannot be extrapolated to other drugs. To overcome the above limitations, we have used an efflux ratio\u2010relative expression factor (ER\u2010REF) approach to successfully predict the fetal\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>p,uu<\/jats:sub>\n                    of P\u2010gp substrates. Because many drugs taken by pregnant people are also BCRP substrates, here, we extend this approach to drugs that are effluxed by both placental BCRP and P\u2010gp or P\u2010gp alone. To verify our predictions, we chose drugs for which UV\/MP data were available at term: glyburide and imatinib (both BCRP and P\u2010gp substrates) and nelfinavir (only P\u2010gp substrate). First, the ER of the drugs was determined using Transwells and MDCKII cells expressing either BCRP or P\u2010gp. Then, the ER was scaled using the proteomics\u2010informed REF value to predict the fetal\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>p,uu<\/jats:sub>\n                    of the drug at term. The ER\u2010REF predicted fetal\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>p,uu<\/jats:sub>\n                    of glyburide (0.43), imatinib (0.42), and nelfinavir (0.40) fell within two\u2010fold of the corresponding\n                    <jats:italic>in vivo<\/jats:italic>\n                    fetal\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>p,uu<\/jats:sub>\n                    (0.44, 0.37, and 0.46, respectively). These data confirm that the ER\u2010REF approach can successfully predict fetal drug exposure to BCRP\/P\u2010gp and P\u2010gp substrates, at term.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3157","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T01:14:20Z","timestamp":1703121260000},"page":"1044-1053","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Successful Prediction of Fetal Exposure to Dual\n                    <scp>BCRP<\/scp>\n                    \/P\u2010gp Drug Substrates Using the Efflux\n                    <scp>Ratio\u2010Relative<\/scp>\n                    Expression Factor Approach and\n                    <scp>PBPK<\/scp>\n                    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