title: Pharmacokinetics of clomipramine during pregnancy.
abstract: OBJECTIVE
  Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their ratios during pregnancy. Second, we describe Center for Epidemiologic Studies Depression scale (CES-D) scores during pregnancy.
  
  
  METHODS
  During 13 pregnancies, every trimester and 3 months after pregnancy, the clomipramine and desmethylclomipramine concentrations were measured with LC-MSMS and the severity of depression was assessed by taking the CES-D score. All concentrations used in our calculations were in fact the ratio between actual plasma concentration (μg/l) and the actual dose (mg). We compared differences in ratios between trimesters by using the Friedman test.
  
  
  RESULTS
  Studying 12 women and 13 pregnancies, we found no changes in mean clomipramine concentrations, a statistically significant decrease in mean desmethylclomipramine concentrations (p = 0.014) and a significant decrease in the ratio of desmethylclomipramine/clomipramine mean concentrations during pregnancy (p = 0.014) compared to the post-partum period. Sub-therapeutic concentrations of clomipramine and desmethylclomipramine were found in three patients during whole pregnancy.
  
  
  CONCLUSIONS
  The mean concentrations of the pharmacologically active metabolite of clomipramine and desmethylclomipramine changes during pregnancy, where a decrease in mean concentrations was found during pregnancy. In case of recurrent disease, we recommend to control clomipramine and its metabolite concentrations, while both are active.
authors.affiliation: Department of Clinical Pharmacy, Isala Klinieken, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands. p.g.j.ter.horst@isala.nl.|University Centre for Pharmacy, Unit of Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, The Netherlands. p.g.j.ter.horst@isala.nl.
authors.forename: P G J
authors.initials: PG
authors.lastname: Ter Horst
authors.affiliation: University Centre for Pharmacy, Unit of Pharmacokinetics, Toxicology and Targeting, University of Groningen, Groningen, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Proost
authors.affiliation: Department of Psychiatry, Isala Klinieken, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: Smit
authors.affiliation: Department of Clinical Pharmacy, Isala Klinieken, Dr van Heesweg 2, 8025 AB, Zwolle, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Vries
authors.affiliation: University Centre for Pharmacy, Unit of PharmacoEpidemiology and PharmacoEconomics, University of Groningen, Groningen, The Netherlands.
authors.forename: L T W
authors.initials: LT
authors.lastname: de Jong-van de Berg
authors.affiliation: University Centre for Pharmacy, Unit of Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, The Netherlands.|Department of Hospital and Clinical Pharmacy, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Wilffert
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002853:Chromatography, Liquid / Q000379:methods; D002997:Clomipramine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003863:Depression / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000929:Antidepressive Agents, Tricyclic; C012273:desmethylclomipramine; D002997:Clomipramine
keywords: Clomipramine; Desmethylclomipramine; Pregnancy