LAUSR

BACKGROUND Pregnant women have an increased risk of infections, and early and decisive treatment is preferred to prevent complications. Although ciprofloxacin is very commonly used, safety aspects of maternal treatment during pregnancy are limited and avoidance of its use during late pregnancy is recommended. OBJECTIVE The aim is to estimate maternal-to-fetal transfer clearance of ciprofloxacin at a therapeutic concentration and to determine fetal exposure to maternally administered ciprofloxacin. STUDY DESIGN Transplacental pharmacokinetics were determined with the ex vivo placental model, which is a reliable experimental model for estimating fetal drug exposure. Human placentas from uncomplicated term pregnancies were collected after delivery and a suitable cotyledon was cannulated. Ciprofloxacin was added at a therapeutic concentration (1.6 μg/mL) to the maternal compartment and antipyrine was included as a reference drug (10.0 μg/mL). Samples were collected from the maternal and fetal compartment on 12 timepoints (-2 to 180 min) and the integrity and metabolic parameters were measured consecutively. Drug concentrations were determined using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS Five human placentas from healthy term pregnancies were collected after delivery and cannulated with success. Ciprofloxacin crossed the placenta; its mean concentration in the fetal compartment was 0.3 μg/mL, accounting for 22% (0.29/1.30, range 15-31%) of the maternal concentration after 3 h. The fetal/maternal ciprofloxacin concentration ratio increased gradually over time and reached 0.53. The transfer clearance for ciprofloxacin was 0.28 mL/min (range, 0.21-0.41 mL/min) during the first hour and 0.21 mL/min (range, 0.14-0.26 mL/min) during the following 2h. After end perfusion the mean tissue concentration and proportion of ciprofloxacin were 0.7 μg/g and 11% (14/130, range 7-14%), respectively. CONCLUSIONS Ciprofloxacin crossed the placenta at a slow, constant rate, indicating moderate fetal exposure. To our knowledge, this is the first study to verify an accumulation of ciprofloxacin in the placenta that may lengthen the duration of fetal exposure. These Results are an essential element of fetal risk assessment, but further studies are needed to estimate fetal safety.