{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:40:12Z","timestamp":1793227212496,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV\u2010006678"],"award-info":[{"award-number":["INV\u2010006678"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We have previously developed a maternal\u2010fetal physiologically\u2010based pharmacokinetic (m\u2010f PBPK) model to dynamically predict (and verify) fetal\u2010maternal exposure to drugs that passively diffuse across the placenta. Here, we extended the application of this model to dynamically predict fetal exposure to drugs which are effluxed by placental P\u2010glycoprotein, namely the antenatal corticosteroids (ACS; dexamethasone [DEX], and betamethasone [BET]). To do so, we estimated both the placental P\u2010gp mediated efflux clearance (CL) and the passive diffusion CL of the ACS. The efficacy and toxicity of the currently used maternal ACS dosing regimens to prevent neonatal respiratory distress syndrome could be improved by altering their dosing regimens. Therefore, to illustrate the utility of our m\u2010f PBPK model, we used it to design alternative dosing regimens of DEX and BET that could potentially improve their efficacy and reduce their toxicity. The redesigned dosing regimens are convenient to administer, maintain maternal\u2010fetal exposure (area under the concentration\u2010time curve [AUC]) or maximum plasma concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ) or both (DEX and BET) or minimize maternal exposure while maintaining fetal drug plasma concentrations above the minimum therapeutic threshold of 1\u00a0ng\/ml for 48\u00a0h (BET only; based on efficacy data in sheep). To our knowledge, this is the first study to dynamically predict fetal plasma concentrations of placental P\u2010gp effluxed drugs. Our approach and our m\u2010f PBPK model could be used in the future to predict maternal\u2010fetal exposure to any drug and to design alternative dosing regimens of the drug.\n                  <\/jats:p>","DOI":"10.1002\/psp4.12674","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T16:31:36Z","timestamp":1626453096000},"page":"1057-1070","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Estimating fetal exposure to the P\u2010gp substrates, corticosteroids, by PBPK modeling to inform prevention of neonatal respiratory distress syndrome"],"prefix":"10.1002","volume":"10","author":[{"given":"Olena","family":"Anoshchenko","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Washington Seattle USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Milad","sequence":"additional","affiliation":[{"name":"Milad Pharmaceutical Consulting LLC Plymouth Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jashvant D.","family":"Unadkat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Washington Seattle USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.14151"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.117.075192"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.116.073957"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2017-000398"},{"key":"e_1_2_9_6_1","first-page":"CD004454","article-title":"Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth","volume":"3","author":"Roberts D","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.15449"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071152"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.21.2.176"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001711"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2012.03.008"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:PHAM.0000003377.39548.f6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1980.136"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.120250"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1887"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.120.000067"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01060016"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00542353"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2017.11.560"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1438"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.062984"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-019-2206-x"},{"issue":"1","key":"e_1_2_9_23_1","first-page":"12","article-title":"Neonatal respiratory distress syndrome: tackling a worldwide problem","volume":"44","author":"Dyer J","year":"2019","journal-title":"P T"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0308-1"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.110772"},{"issue":"1","key":"e_1_2_9_26_1","first-page":"105","article-title":"Dexamethasone metabolism by human liver in vitro. 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