title: Maternal Pharmacokinetics and Fetal Disposition of (±)-Citalopram during Mouse Pregnancy.
abstract: While selective-serotonin reuptake inhibitor (SSRI) antidepressants are commonly prescribed in the treatment of depression, their use during pregnancy leads to fetal drug exposures. According to recent reports, such exposures could affect fetal development and long-term offspring health. A central question is how pregnancy-induced physical and physiological changes in mothers, fetuses, and the placenta influence fetal SSRI exposures during gestation. In this study, we examined the effects of gestational stage on the maternal pharmacokinetics and fetal disposition of the SSRI (±)-citalopram (CIT) in a mouse model. We determined the maternal and fetal CIT serum concentration-time profiles following acute maternal administration on gestational days (GD)14 and GD18, as well as the fetal brain drug disposition. The results show that pregnancy affects the pharmacokinetics of CIT and that maternal drug clearance increases as gestation progresses. The data further show that CIT and its primary metabolite desmethylcitalopram (DCIT) readily cross the placenta into the fetal compartment, and fetal exposure to CIT exceeds that of the mother during gestation 2 h after maternal administration. Enzymatic activity assays revealed that fetal drug metabolic capacity develops in late gestation, resulting in elevated circulating and brain concentrations of DCIT at embryonic day (E)18. Fetal exposure to the SSRI CIT in murine pregnancy is therefore influenced by both maternal gestational stage and embryonic development, suggesting potential time-dependent effects on fetal brain development.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Velasquez
authors.forename: Nick
authors.initials: N
authors.lastname: Goeden
authors.affiliation: Department of Biology and Chemistry, Azusa Pacific University , Azusa, California 91702, United States.
authors.forename: Skyla M
authors.initials: SM
authors.lastname: Herod
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bonnin
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000187:drug effects*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors
keywords: SSRI; citalopram; fetal brain; placenta; pregnancy