///2017 Abstract Details
2017 Abstract Details2019-08-02T15:54:53-06:00

Pharmacokinetic modeling and placental transfer of ampicillin administered to laboring women

Abstract Number: SAT-41
Abstract Type: Original Research

Amy E Judy MD, MPH1 ; David Drover MD2; Adam Frymoyer MD3; Brendan Carvalho MBBCh4

Background: Ampicillin is used for multiple peripartum indications including prevention of neonatal group beta streptococcus (GBS) and treatment of intrapartum chorioamnionitis. Despite its widespread use in pregnancy, existing pharmacokinetic data for ampicillin does not address current recommended dosing paradigms or indications for use. The aim of this study was to characterize the pharmacokinetic profile and placental transfer of ampicillin administered to laboring women, and to compare these findings to existing pharmacokinetic data.

Methods: Prospective cohort IRB-approved study of pregnant women prescribed intravenous ampicillin for neonatal GBS prevention or chorioamnionitis treatment. Women received a 2-g loading dose with 1-g administered every 4 h (GBS indication), or 2-g loading dose with 2-g every 6 h (chorioamnionitis indication). Maternal blood samples were collected at baseline, 5, 15 and 30 min, mid-point of dosing interval (2-3 h), immediately prior to next dose (4-6 h), and at delivery (MV). Whole blood dried blood spots sampling technique was utilized, and pharmacokinetics were analyzed via a population approach with mixed-effect modeling. Umbilical cord arterial (UA) and venous (UV) blood were sampled at time of delivery, and UA:MV and UA:UV ratios determined.

Results: Pharmacokinetic profiles of 28 women were analyzed. Best fit to the data was with a two-compartment model. Analysis revealed a central volume of distribution (V1) of 81.0 L and clearance (Cl) of 86.2 L/h. Inter-compartmental Cl was 21.1 L/h and peripheral volume of distribution (V2) was 65.6 L. Variation in CL and V1 between patients was large (42% and 54% respectively). Ampicillin concentrations over time are depicted the Figure. The UV:MA and UA:UV ratios were 0.64 ± 0.33 and 0.86 ± 1.00 respectively.

Conclusion:

Our study revealed a V and Cl for ampicillin that is greater than previously published in pregnant and non-pregnant subjects (1,2). The presence of infection may have increased the V and Cl for ampicillin. Prior studies have focused on patients receiving ampicillin for cesarean delivery, and not laboring women or women with acute infections. Results from this study highlight the importance of studying drugs in both the population (pregnant vs. non-pregnant) and indication (laboring, active infection vs. cesarean) of interest.

References:

1. Am J Obstet Gynecol 1993;168:667

2. J Infect Dis 1977;136:370



SOAP 2017