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

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