{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:04:32Z","timestamp":1792681472529,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:p>Antiretroviral therapy during pregnancy reduces the risk of vertical HIV\u20101 transmission. However, drug dosing is challenging as pharmacokinetics (PK) may be altered during pregnancy. We combined a pregnancy physiologically\u2010based pharmacokinetic (PBPK) modeling approach with data on placental drug transfer to simulate maternal and fetal exposure to dolutegravir (DTG). First, a PBPK model for DTG exposure in healthy volunteers was established based on physiological and DTG PK data. Next, the model was extended with a fetoplacental unit using transplacental kinetics obtained by performing <jats:italic>ex vivo<\/jats:italic> dual\u2010side human cotyledon perfusion experiments. Simulations of fetal exposure after maternal dosing in the third trimester were in accordance with clinically observed DTG cord blood data. Furthermore, the predicted fetal trough plasma concentration (C<jats:sub>trough<\/jats:sub>) following 50\u00a0mg q.d. dosing remained above the concentration that results in 90% of viral inhibition. Our integrated approach enables simulation of maternal and fetal DTG exposure, illustrating this to be a promising way to assess DTG PK during pregnancy.<\/jats:p>","DOI":"10.1002\/cpt.1748","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T11:41:23Z","timestamp":1577101283000},"page":"1352-1361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Assessment of Maternal and Fetal Dolutegravir Exposure by Integrating <i>Ex Vivo<\/i> Placental Perfusion Data and Physiologically\u2010Based Pharmacokinetic Modeling"],"prefix":"10.1111","volume":"107","author":[{"given":"Jolien J.M.","family":"Freriksen","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"},{"name":"Department of Pharmacy Radboud Institute for Health Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stein","family":"Schalkwijk","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Radboud Institute for Health Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela P.","family":"Colbers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Radboud Institute for Health Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Abduljalil","sequence":"additional","affiliation":[{"name":"Simcyp Division Certara UK Limited Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans G.M.","family":"Russel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Radboud Institute for Health Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick","family":"Greupink","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Radboud Institute for Molecular Life Sciences Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,24]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"World Health Organization (WHO).Updated recommendations on first\u2010line and second\u2010line antiretroviral regimens and post\u2010exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines<https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/277395\/WHO-CDS-HIV-18.51-eng.pdf?ua=1> (2018). 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