Abstract

Ampicillin is used for multiple peripartum indications including prevention of neonatal group beta streptococcus (GBS) and treatment of chorioamnionitis. Despite its widespread use in obstetrics, existing pharmacokinetic data for ampicillin do not address contemporary indications or dosing paradigms for this population. We sought to characterize the pharmacokinetic profile of ampicillin administered to laboring women.Using whole blood dried blood spot sampling technique, maternal blood samples were collected at specified times from 31 women receiving IV ampicillin for peripartum indications. Women received either a 2-g loading dose with 1-g administered every 4 h (GBS), or 2-g every 6 h (chorioamnionitis). Pharmacokinetics were analyzed via a population approach with non-linear mixed-effect modeling.The data were best described by a two-compartment model with first-order elimination, with the following whole blood parameters: central volume of distribution (V1) 75.2 L (95% CI 56.3-93.6), clearance (CL) 82.4 L/h (95% CI 59.7-95.7), inter-compartmental clearance (Q) 20.9 L/h (95% CI 16.2-38.2), and peripheral volume of distribution (V2) 61.1 L (95% CI 26.1-310.5). Inter-patient variation in CL and V1 was large (42.0% and 56.7% respectively). Simulations of standard dosing strategies demonstrated over 98% of women are predicted to achieve an estimated free plasma concentration above MIC 0.5 mcg/mL for more than 50% of the dosing interval.Although large variation in the pharmacokinetics of ampicillin in pregnant women exists, as predicted by our model, current standard dosing strategies achieve adequate exposure for GBS in nearly all patients.

View details for DOI 10.1055/a-1674-6394

View details for PubMedID 34670320