title: Concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during pregnancy.
abstract: OBJECTIVE
  Depression during pregnancy is common and includes risks for mother and child. Pharmacokinetics of venlafaxine may be changed during pregnancy. This study aimed to describe changes in metabolic ratios and concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during and after pregnancy.
  
  
  METHODS
  To study this, we used data from our study of compliance to Antidepressants During Pregnancy (the ADAP study) to investigate the course of venlafaxine and O-desmethylvenlafaxine concentrations during pregnancy and in the period post-partum.
  
  
  CONCLUSIONS
  We found that the venlafaxine concentration significantly changed during pregnancy when compared to the post-partum period (P = 0·028). The median concentration of venlafaxine in the first trimester was 98·9% (54·2-292·0%), the second 100·0% (46·5-264·0%) and the third trimester 87·0% (61·5-217·2%). We did not found differences in O-desmethylvenlafaxine concentrations in the different trimesters of pregnancy compared with the post-partum period, P = 0·565. Also the ratio of O-desmethylvenlafaxine/venlafaxine concentrations increased significantly from 76·9% (range 32·8-142·0%) in the first trimester to 196·7% (range 83·3-427·6%) in the third trimester compared with the post-partum period, P = 0·004. Further, three of seven patients had concentrations below the therapeutic reference range (100-400 μg/L) in any period of pregnancy, whereas no one had subtherapeutic concentrations in the post-partum period.
  
  
  CONCLUSIONS
  Venlafaxine concentrations decreases during pregnancy, and the ratio of the concentrations of O-desmethylvenlafaxine/venlafaxine increases during pregnancy. Pregnant women using venlafaxine are at risk for subtherapeutic concentrations, therefore routine monitoring of concentrations venlafaxine and O-desmethylvenlafaxine is recommendable during pregnancy.
authors.affiliation: Department of Clinical Pharmacy, Isala, Zwolle, The Netherlands.
authors.forename: P G J
authors.initials: PG
authors.lastname: ter Horst
authors.forename: K H M
authors.initials: KH
authors.lastname: Larmené-Beld
authors.forename: J
authors.initials: J
authors.lastname: Bosman
authors.forename: E L
authors.initials: EL
authors.lastname: van der Veen
authors.forename: A
authors.initials: A
authors.lastname: Wieringa
authors.forename: J P
authors.initials: JP
authors.lastname: Smit
mesh_terms: D000328:Adult; D003511:Cyclohexanols / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D000069468:Desvenlafaxine Succinate; D005260:Female; D006801:Humans; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy / Q000378:metabolism*; D011256:Pregnancy Outcome; D011264:Pregnancy Trimesters / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D000069468:Desvenlafaxine Succinate; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride
keywords: O-desmethylvenlafaxine; pharmacokinetics; pregnancy; venlafaxine