Disposition of Chiral and Racemic Fluoxetine and Norfluoxetine Across Childbearing

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.