Abstract
Objective Ampicillin is used for multiple peripartum indications including prevention of neonatal
group B 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.
Study Design Using whole blood dried blood spot sampling technique, maternal blood samples were
collected at specified times from 31 women receiving intravenous (IV) ampicillin for
peripartum indications. Women received either a 2-g loading dose with 1-g administered
every 4 hours (GBS) or 2-g every 6 hours (chorioamnionitis). Pharmacokinetics were
analyzed via a population approach with nonlinear mixed-effect modeling.
Results 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% confidence interval [CI]: 56.3–93.6); clearance (CL), 82.4 L/h (95%
CI: 59.7–95.7); intercompartmental 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). Interpatient 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 mean inhibitory concentration (MIC) of 0.5 μg/mL for more than 50% of the dosing
interval.
Conclusion 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.
Key Points
-
IV ampicillin is widely used in obstetrics.
-
Pharmacokinetic studies are lacking.
-
Ampicillin pharmacokinetics were established.
-
Ampicillin clearance and volume of distribution are high.
-
Current ampicillin dosing strategies are sufficient.
Keywords
antibiotics - pharmacokinetics - placenta - ampicillin - obstetrics - pregnant - dried
blood spot sampling - group B streptococcus
