Pregnancy exposure to quetiapine - Therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood and obstetrical outcomes

Schizophr Res. 2018 May:195:252-257. doi: 10.1016/j.schres.2017.09.043. Epub 2017 Sep 29.

Abstract

Rationale: This prospective study is the first to measure and correlate quetiapine concentrations in maternal blood, amniotic fluid and umbilical cord blood to account for the distribution of quetiapine.

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

Results: The median daily dosage of quetiapine was 300mg (Q1: 300mg, Q3: 600mg, range 200-800mg). There was a strong and significant correlation between maternal serum and cord blood concentrations (r=0.893, p=0.007). The median penetration ratio into fetal circulation was 0.18 (Q1: 0.16, Q3: 0.32; range 0.13-0.42), suggesting a low penetration. The median penetration ratio into amniotic fluid was 0.44 (Q1: 0.15, Q3: 0.96; range 0.09-1.70).

Conclusions: Quetiapine concentrations in amniotic fluid and cord blood give evidence that quetiapine is constantly accessible to the fetus with a relatively low penetration ratio. A high correlation between maternal serum and umbilical cord blood concentrations highlights a predictive role of quantifying drug concentrations in maternal serum for assessing drug concentrations in fetal circulation. Findings support the important role of therapeutic drug monitoring in supporting the efficacy and safety of psychopharmacological treatment strategies in highly vulnerable populations.

Keywords: Amniotic fluid; Antipsychotics; Cord blood; Pharmacokinetics; Placental transfer; Pregnancy; Psychosis; Quetiapine; Therapeutic drug monitoring.

MeSH terms

  • Adult
  • Amniotic Fluid / metabolism*
  • Antipsychotic Agents / adverse effects*
  • Drug Monitoring
  • Female
  • Fetal Blood
  • Humans
  • Infant
  • Male
  • Pregnancy
  • Pregnancy Complications / chemically induced*
  • Prenatal Exposure Delayed Effects / blood*
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Quetiapine Fumarate / adverse effects*
  • Young Adult

Substances

  • Antipsychotic Agents
  • Quetiapine Fumarate