PMID- 26765210
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20221207
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Linking)
VI  - 7
IP  - 3
DP  - 2016 Mar 16
TI  - Maternal Pharmacokinetics and Fetal Disposition of (+/-)-Citalopram during Mouse 
      Pregnancy.
PG  - 327-38
LID - 10.1021/acschemneuro.5b00287 [doi]
AB  - 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.
FAU - Velasquez, Juan C
AU  - Velasquez JC
FAU - Goeden, Nick
AU  - Goeden N
FAU - Herod, Skyla M
AU  - Herod SM
AD  - Department of Biology and Chemistry, Azusa Pacific University , Azusa, California 
      91702, United States.
FAU - Bonnin, Alexandre
AU  - Bonnin A
LA  - eng
GR  - R01 MH106806/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20160130
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0DHU5B8D6V (Citalopram)
SB  - IM
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Citalopram/*pharmacokinetics/toxicity
MH  - Female
MH  - Fetus/*drug effects
MH  - Mice
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Selective Serotonin Reuptake Inhibitors/*pharmacokinetics/toxicity
PMC - PMC5384759
OTO - NOTNLM
OT  - SSRI
OT  - citalopram
OT  - fetal brain
OT  - placenta
OT  - pregnancy
COIS- The authors declare no competing financial interest.
EDAT- 2016/01/15 06:00
MHDA- 2016/12/15 06:00
PMCR- 2017/04/07
CRDT- 2016/01/15 06:00
PHST- 2016/01/15 06:00 [entrez]
PHST- 2016/01/15 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2017/04/07 00:00 [pmc-release]
AID - 10.1021/acschemneuro.5b00287 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2016 Mar 16;7(3):327-38. doi: 10.1021/acschemneuro.5b00287. 
      Epub 2016 Jan 30.