Maternal Pharmacokinetics and Fetal Disposition of (±)-Citalopram during Mouse Pregnancy

ACS Chemical Neuroscience
Juan C VelasquezAlexandre Bonnin

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 dr...Continue Reading

References

Aug 1, 1997·Cell and Tissue Research·G BrüningH G Baumgarten
Nov 14, 1997·Clinical Pharmacology and Therapeutics·M WadeliusA Rane
Dec 10, 1997·Clinical Pharmacokinetics·R LoebsteinG Koren
Oct 6, 1998·Journal of Pharmaceutical Sciences·A C HeatheringtonH Golde
Nov 24, 1998·The Journal of Comparative Neurology·C LebrandP Gaspar
Feb 16, 2000·Pharmacology & Therapeutics·C Hiemke, S Härtter
Jul 4, 2001·Nature Reviews. Genetics·J Rossant, J C Cross
Aug 4, 2001·BMJ : British Medical Journal·J EvansJ Golding
Jan 22, 2002·Best Practice & Research. Clinical Obstetrics & Gynaecology·M Dawes, P J Chowienczyk
Jan 24, 2002·The Journal of Pharmacology and Experimental Therapeutics·Ronald N Hines, D Gail McCarver
Jan 31, 2002·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·N EjiriK Doi
Aug 22, 2002·Clinical Pharmacology and Therapeutics·Tuija HeikkinenKari Laine
Sep 25, 2002·BJOG : an International Journal of Obstetrics and Gynaecology·Tuija HeikkineKari Laine
Apr 24, 2003·Clinical Pharmacology and Therapeutics·Tuija HeikkinenKari Laine
May 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Malika El YacoubiJean-Marie Vaugeois
Feb 17, 2005·Experimental and Molecular Pathology·Noriko EjiriKunio Doi
Jul 15, 2005·Journal of Perinatology : Official Journal of the California Perinatal Association·Keri A LattimoreDelia M Vazquez
Sep 24, 2005·Clinical Pharmacokinetics·Gail D Anderson
Feb 2, 2006·JAMA : the Journal of the American Medical Association·Lee S CohenZachary N Stowe
Mar 24, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·James J CrowleyIrwin Lucki
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Denis EvseenkoJeffrey A Keelan
Apr 24, 2007·Nature Neuroscience·Alexandre BonninPat Levitt
Jun 6, 2007·American Journal of Obstetrics and Gynecology·William O CooperWayne A Ray
Jan 4, 2008·The New England Journal of Medicine·R H Belmaker, Galila Agam
Jul 12, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·D A MrazekR M Weinshilboum
Jul 25, 2008·BJOG : an International Journal of Obstetrics and Gynaecology·T DeaveA Emond
Nov 18, 2008·Journal of Clinical Psychopharmacology·Marlene P FreemanFrancisco Moreno
Sep 12, 2009·Clinical Pharmacokinetics·F F Tessa VerversAlfred F A M Schobben
Sep 30, 2009·Expert Opinion on Drug Metabolism & Toxicology·Päivi MyllynenKirsi Vähäkangas

❮ Previous
Next ❯

Citations

Jan 12, 2017·ACS Chemical Neuroscience·Jennifer R KingAlexandre Bonnin
Jun 29, 2017·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Jenna L N SprowlesCharles V Vorhees
Aug 23, 2020·International Journal of Molecular Sciences·Sabrina I HanswijkJudith R Homberg
Jun 12, 2019·ACS Chemical Neuroscience·Juan C VelasquezAlexandre Bonnin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.