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Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8\u2009mg intravenously within 4\u2009h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07\u2009mg\/kg orally once every 24\u2009h for up to five doses. Using current PK data, model parameters from a two\u2010compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis\u2010Hastings Markov\u2010chain Monte Carlo estimation algorithm in NONMEM. The updated Bayesian model indicated a slower absorption rate (KA) but no differences in model parameters (CL, V, V2, Q) after including body weight and postmenstrual age. Sensitivity analyses on CL prior revealed statistical improvement favoring larger body weights, but not changes in postmenstrual age. However, further model development using larger body weights did not illustrate superior performance through visual inspection of diagnostic plots. Overall, a cumulative AUC of at least 1000\u2009ng*h\/mL appears to be the threshold for reductions in symptom severity. Exposure\u2010response analyses suggest the total number of doses to be the primary driver for efficacy with respect to AUC, which reasonably aligns with the literature. Overall, it is suggested that at least three doses of the current oral ondansetron regimen are required to reduce symptom severity in neonates.<\/jats:p>","DOI":"10.1111\/cts.70147","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T03:19:22Z","timestamp":1739243962000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bayesian Population Pharmacokinetic Modeling of Ondansetron for Neonatal Opioid Withdrawal Syndrome"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9838-613X","authenticated-orcid":false,"given":"Kevin","family":"Lam","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"Mondick","sequence":"additional","affiliation":[{"name":"A2\u2010Ai  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6191-7697","authenticated-orcid":false,"given":"Gary","family":"Peltz","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Pain and Perioperative Medicine Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-3081","authenticated-orcid":false,"given":"Manhong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Pain and Perioperative Medicine Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5074-0141","authenticated-orcid":false,"given":"Walter K.","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2021.12.021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.24991"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2023\u2010062871"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7006a4"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020\u2010029074"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.13537"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41372\u2010021\u201001206\u20103"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e328322e73d"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/00952990.2016.1210614"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.5"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2023.12.020"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2981"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41372\u2010022\u201001487\u20102"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13440"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010020\u201009695\u2010z"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13088"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010009\u20100730\u20108"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000369"},{"key":"e_1_2_9_20_1","unstructured":"S. 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