Transplacental passage of ampicillin: Implications for antenatal therapy

INTRODUCTION: Bacterial infections during pregnancy can endanger both mother and fetus, leading to premature rupture of membranes, chorioamnionitis, preterm birth, and neonatal sepsis. Effective antibiotic therapy must ensure sufficient exposure. Ampicillin is widely used in pregnancy, particularly against group B streptococcus (GBS) and E. coli, but its pharmacokinetics, including placental transfer, are not fully understood. This study evaluated ampicillin's transplacental transfer using an ex vivo placenta dual-side perfusion model and assessed maternal serum concentrations in pregnant women undergoing therapy. MATERIALS AND METHODS: Six placentas were perfused with 50 or 100 mg/L ampicillin. Ampicillin concentrations were assessed both in the maternal and fetal circuits every 30 min during a period of 4 h. Additionally, maternal serum samples from six pregnant women (gestational age: 24 + 4 to 33 + 0) receiving 2 g ampicillin intravenously were analyzed every 30 min up to 4 h post-administration. Antibiotic concentrations were determined using LC-MS. RESULTS: Concentrations determined in the maternal perfusion circuit were 33.4 ± 15.9 and 41.2 ± 5.8 mg/L, as well as 15.4 ± 4.5 and 25.3 ± 19.9 mg/L in the fetal circuit. The transfer rate was about 25 % after 4 h of perfusion. Maternal serum concentrations at 30 min reached 54.1 ± 6.4 mg/L and declined to 2.3 ± 1.6 mg/L at 4 h. DISCUSSION: This study using an ex vivo placenta perfusion model, revealed only moderate transplacental transfer of ampicillin. This finding, in the context of the retrieved serum concentrations, suggests that adjusted dosing may be required in severe conditions to optimize drug exposure, emphasizing the need for further pharmacokinetic research in pregnancy.