Obura, B 
ORCID: 0000-0002-8885-1795, Unsworth, J, Jimenez-Valverde, A, Waitt, C ORCID: 0000-0003-0134-5855, Das, S ORCID: 0000-0002-2540-4816, Hope, W ORCID: 0000-0001-6187-878X and Navaratnam, K
(2025)
Pharmacokinetics of Intrapartum Benzylpenicillin: Insights Into Candidate Regimens to Prevent Early Onset Neonatal Group B Streptococcus Disease
Cpt Pharmacometrics and Systems Pharmacology, 14 (9).
pp. 1504-1514.
ISSN 2163-8306, 2163-8306
Abstract
Early onset neonatal Group B Streptococcus (GBS) infection accounts for significant global morbidity and mortality. Intrapartum prophylaxis with benzylpenicillin is advised for women at high risk of having a baby affected by early onset GBS disease. Pregnancy-related physiological changes can alter pharmacokinetics. To estimate the intrapartum pharmacokinetics of penicillin, women (n = 12) at risk of GBS disease were enrolled. A fixed regimen of intravenous benzylpenicillin 3 g at onset of labor and 1.5 g every 4 h 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 (fC<inf>min</inf> > MIC for 100% of the dosing interval) were determined using Monte Carlo simulation. Benzylpenicillin pharmacokinetics were well described using a two-compartment model with a linked umbilical cord compartment. The mean volume of the central compartment and first-order clearance were 16.55 L and 41.24 L/h, respectively. Simulations showed that a lower regimen of benzylpenicillin 2.4 g followed by 1.2 g every 4 h resulted in adequate drug exposure—with plasma fC<inf>min</inf> > 0.125 mg/L for 100% of the dosing interval in > 90% 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | benzylpenicillin, group B Streptococcus, neonatal, penicillin, pharmacokinetics, phenoxymethylpenicillin |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 16 Jul 2025 08:42 |
| Last Modified: | 28 Feb 2026 01:28 |
| DOI: | 10.1002/psp4.70072 |
| Open Access URL: | https://ascpt.onlinelibrary.wiley.com/doi/10.1002/... |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3193740 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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