Pregnancy exposure to citalopram - Therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood

Abstract

Rationale: Aim of the study was to measure and correlate citalopram concentrations in maternal blood, amniotic fluid and umbilical cord blood to account for the distribution of the drug between these three compartments.

Methods: Concentrations of citalopram were measured in twelve mother infant pairs at the time of delivery. Data are provided as median values, first (Q1) and third (Q3) quartiles as well as ranges. To account for the penetration ratio into amniotic fluid and cord blood, the concentration of citalopram in was divided by the concentration in maternal serum. Correlations between daily dosage, maternal serum concentrations and umbilical cord blood concentrations were computed for twelve patients. As amniotic fluid was only available for nine mother infant pairs, appropriate calculations are provided for these mother-infant pairs.

Results: The median daily dosage of citalopram was 20mg (Q1: 10mg, Q3: 20mg; range 10-40mg). The relation between the daily dosage of citalopram and its concentrations in maternal serum was highly significant (r=0.667, p=0.018). Maternal serum concentrations and cord blood concentrations were positively correlated (r=0.790, p=0.002) with a median penetration ratio into the fetal circulation of 0.78 (Q1: 0.52, Q3: 1.16, range 0.46-1.66). The median penetration ratio into amniotic fluid was 1.8 (Q1: 1.07, Q3: 2.64; range 0.52-6.97).

Conclusions: Citalopram concentrations in amniotic fluid and cord blood give evidence that maternally administered citalopram is constantly accessible to the fetus via amniotic fluid. A high correlation between maternal serum concentrations of citalopram and umbilical cord blood concentrations highlights a predictive role of quantifying drug concentrations in maternal serum for assessing drug concentrations in the fetal circulation. Findings support the important role of therapeutic drug monitoring in maintaining the safety of pregnant women and exposed infants.

Keywords: Amniotic fluid; Antidepressants; Citalopram; Cord blood; Depression; Pharmacokinetics; Placental transfer; Pregnancy; Therapeutic drug monitoring.