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There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. We developed a generic physiologically\u2010based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure. Drug\u2010specific model inputs were parameterized using data from the literature. Population\u2010specific inputs were derived from a previously conducted systematic literature review of anatomic and physiologic changes in postpartum women. Model predictions were evaluated using ondansetron plasma and breast milk concentration data collected prospectively from 78 women in the Commonly Used Drugs During Lactation and infant Exposure (CUDDLE) study. The final model predicted breast milk and plasma exposures following a single 4\u00a0mg dose of intravenous ondansetron in 1,000 simulated women who were 2\u00a0days postpartum. Model predictions showed good agreement with observed data. Breast milk median prediction error (MPE) was 18.4% and median absolute prediction error (MAPE) was 53.0%. Plasma MPE was 32.5% and MAPE was 43.2%. The model\u2010predicted daily and relative infant doses were 0.005\u00a0mg\/kg\/day and 3.0%, respectively. This model adequately predicted ondansetron passage into breast milk. The calculated low relative infant dose indicates that mothers receiving ondansetron can safely breastfeed. The model building blocks and population database are open\u2010source and can be adapted to other drugs.<\/jats:p>","DOI":"10.1002\/cpt.2530","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T09:49:33Z","timestamp":1643104173000},"page":"1111-1120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Development of a Generic Physiologically\u2010Based Pharmacokinetic Model for Lactation and Prediction of Maternal and Infant Exposure to Ondansetron via Breast Milk"],"prefix":"10.1111","volume":"111","author":[{"given":"Kathleen M.","family":"Job","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Department of Pediatrics The University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Dallmann","sequence":"additional","affiliation":[{"name":"Pharmacometrics\/Modeling &amp; Simulation Research &amp; Development Bayer AG  Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Parry","sequence":"additional","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine Perelman School of Medicine of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Saade","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch\u2013Galveston  Galveston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Haas","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenna","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Berens","sequence":"additional","affiliation":[{"name":"McGovern Medical School The University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"The Emmes Company, LLC  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Fu","sequence":"additional","affiliation":[{"name":"The Emmes Company, LLC  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Humphrey","sequence":"additional","affiliation":[{"name":"The Emmes Company, LLC  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hornik","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Balevic","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanecia","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Watt","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Pediatrics The University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-017-3750-1"},{"key":"e_1_2_10_3_1","first-page":"897","article-title":"Continuing drug therapy while breastfeeding. 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