The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations

J Clin Psychiatry. 2003 Jan;64(1):73-80. doi: 10.4088/jcp.v64n0114.

Abstract

Background: The purpose of this study was to attain a new landmark in the area of selective serotonin reuptake inhibitor therapy during lactation by establishing a basis for interpreting infant serum concentrations and for minimizing infant exposure in the absence of treatment-emergent side effects.

Method: Breast milk and paired maternal and infant sera were collected following maternal treatment with sertraline monotherapy (25-200 mg/day) administered once daily. Sertraline and its major metabolite were measured in breast milk and serum samples using high-performance liquid chromatography with UV detection (limit of detection = 2 ng/mL).

Results: Twenty-six nursing women with DSM-IV major depressive disorder participated in the study; the mean (SD) daily sertraline dose was 123.9 (62.8) mg/day. Fifteen women submitted 182 breast milk samples for analysis of gradient (foremilk to hindmilk) and time course of medication excretion. The milk/plasma ratio was highly variable (range, 0.42-4.81). A significant gradient and time course of excretion for both sertraline (p <.001 for both) and desmethylsertraline (p <.001 for gradient and p <.046 for time course) were observed, with the highest concentrations observed in the hindmilk 8 to 9 hours after maternal ingestion. Mathematical modeling of sertraline and desmethylsertraline excretion revealed that discarding breast milk 9 hours after maternal dose decreased the infant daily dose of sertraline by a mean of 17.1% (1.8%). Twenty-two mother/infant sera pairs were obtained. Sertraline was detectable in 4 infants (18% of sample), and desmethylsertraline was found in 11 infants (50% of sample). The mean (SD) maximum calculated nursing infant dose of sertraline, 0.67 (0.61) mg/day, and desmethylsertraline, 1.44 (1.36) mg/day, represented 0.54% (0.49%) of the maternal daily dose. The maximum infant dose of desmethylsertraline (p <.002) significantly correlated with infant serum desmethylsertraline concentrations (ng/mL). In contrast, maternal daily dose, duration of medication exposure, and infant age and weight at sampling did not correlate with either detectability (< 2 ng/mL vs. > or = 2 ng/mL) or absolute concentrations (ng/mL) in infant serum. No adverse events were reported or documented in any infant.

Conclusion: These results extend previous studies by demonstrating the utility of breast milk analysis in interpreting infant serum concentrations and minimizing infant exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Feeding* / adverse effects
  • Child Development / physiology
  • Chromatography, High Pressure Liquid
  • Depressive Disorder / blood
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / metabolism
  • Female
  • Humans
  • Infant, Newborn / blood*
  • Infant, Newborn / metabolism
  • Lactation / blood
  • Milk, Human / chemistry*
  • Milk, Human / metabolism
  • Pregnancy
  • Serotonin Uptake Inhibitors / analysis*
  • Serotonin Uptake Inhibitors / blood
  • Serotonin Uptake Inhibitors / pharmacokinetics*
  • Sertraline / analogs & derivatives*
  • Sertraline / analysis*
  • Sertraline / blood
  • Sertraline / pharmacokinetics*

Substances

  • Serotonin Uptake Inhibitors
  • desmethylsertraline
  • Sertraline