{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:07:21Z","timestamp":1784549241899,"version":"3.55.0"},"reference-count":72,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ceftriaxone is a critical antibiotic for treating severe infections during pregnancy, including community\u2010acquired pneumonia, urinary tract infections, gonorrhea, and syphilis, yet optimal dosing remains undefined due to limited pharmacokinetic data in this population. This study developed and validated a physiologically based pharmacokinetic model for ceftriaxone in pregnant women using the open\u2010source Open Systems Pharmacology Suite. A healthy adult model was first calibrated using data from 193 subjects across multiple studies with doses ranging from 500 to 3000 mg, demonstrating acceptable predictive performance with all simulated\u2010to\u2010observed ratios for maximum concentration (0.60\u20100.95) and area under the curve (0.64\u20100.99) falling within accepted 2\u2010fold boundaries. The model was extended to pregnancy by incorporating gestational age\u2010dependent physiological changes, with pregnancy\u2010specific calibration showing excellent agreement (simulated\u2010to\u2010observed ratios of 1.00 for maximum concentration and 0.99 for area under the curve). Population simulations comparing non\u2010pregnant adults to pregnant women at 35 weeks of gestation revealed a 17% reduction in overall exposure and 38% decrease in trough concentrations. Pharmacodynamic target attainment analysis showed that both 1 and 2\u00a0g once\u2010daily intravenous regimens maintained 100%  against\n                    <jats:italic>Treponema pallidum<\/jats:italic>\n                    (MIC =\u00a00.0025 \u00b5g\/mL) throughout pregnancy. Nevertheless, the 38% trough reduction translated to a corresponding decrease in the 100%  breakpoint (2.81\u21921.75 \u00b5g\/mL at 1\u00a0g q.d.; 5.61\u21923.50 \u00b5g\/mL at 2\u00a0g q.d.), quantifying the pharmacodynamic margin under standard regimens. This transparent, reproducible modeling framework provides quantitative support for reconsidering pregnancy dosing strategies and advances precision medicine approaches in obstetric pharmacotherapy during the ongoing maternal syphilis public health crisis.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70205","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:20:07Z","timestamp":1778743207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Physiologically Based Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Analysis for Ceftriaxone Dosing in Pregnant Women: Model Development and Clinical Applications"],"prefix":"10.1002","volume":"66","author":[{"given":"Xinyue","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Environmental and Global Health College of Public Health and Health Professions University of Florida  Gainesville FL USA"},{"name":"Center for Environmental and Human Toxicology University of Florida  Gainesville FL USA"},{"name":"Center for Pharmacometrics and Systems Pharmacology University of Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-8366","authenticated-orcid":false,"given":"Zhoumeng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Environmental and Global Health College of Public Health and Health Professions University of Florida  Gainesville FL USA"},{"name":"Center for Environmental and Human Toxicology University of Florida  Gainesville FL USA"},{"name":"Center for Pharmacometrics and Systems Pharmacology University of Florida  Orlando FL 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Updated February 26 2026. Accessed February 26 2026.https:\/\/clinicaltrials.gov\/study\/NCT07207876."},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7246e1"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/inthealth\/ihad087"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70205","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70205","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:36:10Z","timestamp":1784547370000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":72,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/jcph.70205"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70205","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70205"}}