title: Disposition of chiral and racemic fluoxetine and norfluoxetine across childbearing.
abstract: OBJECTIVE
  To add to the limited data on the clinical pharmacology of antidepressants during pregnancy, we examined the dose-corrected chiral and racemic levels (level/dose) of fluoxetine (FLX) and norfluoxetine (NorFLX) during pregnancy and early postpartum.
  
  
  METHODS
  The authors evaluated 17 pregnant women who received fluoxetine therapy. Doses were recorded weekly across gestation and postpartum. At 20, 30, and 36 weeks of gestation, during delivery, and 12 weeks after delivery, the depression level was assessed with the Hamilton Rating Scale for Depression (HRS-D), and plasma samples were analyzed for levels of S- and R-FLX and S- and R-NorFLX.
  
  
  RESULTS
  The mean ratios of the chiral parent drug (S-FLX + R-FLX) to metabolite levels (S-NorFLX + R-NorFLX) decreased across pregnancy. The differences were significant between 20-36 weeks and 30-36 weeks. After delivery, the mean dose-corrected level of the active moiety S-FLX and the mean ratio of the chiral parent drug (S-FLX + R-FLX) to metabolite level (S-NorFLX + R-NorFLX) significantly increased between delivery and 12 weeks postpartum. Most of the fluoxetine-treated subjects experienced remitted depressive episodes and euthymic mood levels during pregnancy and postpartum.
  
  
  CONCLUSIONS
  The findings extend earlier reports of increased antidepressant metabolism during pregnancy and refractory metabolism after delivery. These data may inform treatment decisions related to dosing in patients who receive fluoxetine during pregnancy.
authors.affiliation: Women's Behavioral HealthCARE, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Sit
authors.forename: James M
authors.initials: JM
authors.lastname: Perel
authors.forename: James F
authors.initials: JF
authors.lastname: Luther
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Helsel
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Wisner
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D049590:Postpartum Period; D011247:Pregnancy; D011248:Pregnancy Complications; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011569:Psychiatric Status Rating Scales; D013237:Stereoisomerism
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; C036139:norfluoxetine