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Pregnancy\u2010related physiological changes can alter pharmacokinetics. To estimate the intrapartum pharmacokinetics of penicillin, women (<jats:italic>n<\/jats:italic>\u2009=\u200912) at risk of GBS disease were enrolled. A fixed regimen of intravenous benzylpenicillin 3\u2009g at onset of labor and 1.5\u2009g every 4\u2009h until delivery was used. Benzylpenicillin concentrations in plasma and umbilical cord were quantified. A nonparametric population pharmacokinetic model was fitted to the data and regimens that optimized drug exposure (<jats:italic>f<\/jats:italic>C<jats:sub>min<\/jats:sub>\u2009&gt;\u2009MIC for 100% of the dosing interval) were determined using Monte Carlo simulation. Benzylpenicillin pharmacokinetics were well described using a two\u2010compartment model with a linked umbilical cord compartment. The mean volume of the central compartment and first\u2010order clearance were 16.55\u2009L and 41.24\u2009L\/h, respectively. Simulations showed that a lower regimen of benzylpenicillin 2.4\u2009g followed by 1.2\u2009g every 4\u2009h resulted in adequate drug exposure\u2014with plasma <jats:italic>f<\/jats:italic>C<jats:sub>min<\/jats:sub> &gt;\u20090.125\u2009mg\/L for 100% of the dosing interval in &gt;\u200990% of the simulated population. Simulations of a continuous infusion of benzylpenicillin resulted in higher target attainment rates when compared to intermittent dosing. Alternative intrapartum regimens of penicillin that are efficacious but require less total daily drug amounts appear feasible. Further research evaluating alternative regimens on clinical outcomes is required.<\/jats:p>","DOI":"10.1002\/psp4.70072","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T12:40:32Z","timestamp":1752064832000},"page":"1504-1514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics of Intrapartum Benzylpenicillin: Insights Into Candidate Regimens to Prevent Early Onset Neonatal Group B <i>Streptococcus<\/i> Disease"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8885-1795","authenticated-orcid":false,"given":"Bonniface","family":"Obura","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Unsworth","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Jimenez\u2010Valverde","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0134-5855","authenticated-orcid":false,"given":"Catriona","family":"Waitt","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health University of Liverpool  Liverpool UK"},{"name":"Infectious Diseases Institute, Makerere University College of Health Sciences  Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-4816","authenticated-orcid":false,"given":"Shampa","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6187-878X","authenticated-orcid":false,"given":"William","family":"Hope","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Navaratnam","sequence":"additional","affiliation":[{"name":"Fetal Medicine Unit Liverpool Women's Hospital  Liverpool UK"},{"name":"Harris\u2010Wellbeing Research Centre University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix656"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102748"},{"issue":"12","key":"e_1_2_9_4_1","first-page":"e280","article-title":"On Behalf of the Royal College of Obstetricians and Gynaecologists. 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