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Pharmacokinetics of Intrapartum Benzylpenicillin: Insights Into Candidate Regimens to Prevent Early Onset Neonatal
Bonniface Obura1, Jennifer Unsworth1, Ana Jimenez-Valverde1
1Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Insights
Intrapartum benzylpenicillin prophylaxis for Group B Streptococcus (GBS) infection in newborns can be optimized. Simulations suggest lower penicillin doses or continuous infusion improve drug exposure, potentially reducing GBS disease burden.
Area of Science:
- Pharmacology
- Obstetrics
- Neonatal Health
Background:
- Early onset neonatal Group B Streptococcus (GBS) infection causes significant global morbidity and mortality.
- Intrapartum benzylpenicillin prophylaxis is recommended for high-risk pregnancies to prevent GBS disease.
- Physiological changes during pregnancy can affect drug pharmacokinetics, necessitating optimized dosing.
Purpose of the Study:
- To estimate the intrapartum pharmacokinetics of benzylpenicillin in women at risk of GBS disease.
- To determine optimized intrapartum penicillin regimens for effective GBS prophylaxis.
- To evaluate alternative dosing strategies for improved drug exposure.
Main Methods:
- A population pharmacokinetic model was developed using data from 12 women receiving a fixed intrapartum benzylpenicillin regimen.
- Plasma and umbilical cord concentrations of benzylpenicillin were quantified.
- Monte Carlo simulations were used to determine regimens optimizing drug exposure (fCmin > MIC for 100% of the dosing interval).
Main Results:
- Benzylpenicillin pharmacokinetics were well described by a two-compartment model with a linked umbilical cord compartment.
- Simulations indicated a reduced regimen (2.4g followed by 1.2g every 4h) achieved adequate drug exposure in over 90% of simulated cases.
- Continuous infusion of benzylpenicillin demonstrated higher target attainment rates than intermittent dosing.
Conclusions:
- Alternative intrapartum penicillin regimens that are efficacious with lower total daily doses appear feasible.
- Optimized dosing strategies, including continuous infusion, may enhance benzylpenicillin's effectiveness in GBS prophylaxis.
- Further research is needed to evaluate the clinical outcomes of alternative intrapartum penicillin regimens.
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 (fCmin > 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 fCmin > 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.
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