DISTRIBUTION AND EXCRETION OF SERTRALINE AND N-DESMETHYLSERTRALINE INHUMAN-MILK

Aims To characterise milk/plasma (M/P) ratio and infant exposure, for sertraline and N-desmethylsertraline, in breast-feeding women taking s ertraline for the treatment of depression. Methods Eight women (mean a ge 28 years) taking sertraline (1.05 mg kg(-1) day(-1)) and their infa nts (mean age 5.7 months) were studied. Sertraline and N-desmethylsert raline in plasma and milk were measured by high-performance liquid chr omatography over a 24 h dose interval at steady-state. M/P values were estimated from area under the plasma and milk concentration-time curv es. AU milk produced was collected over the dose interval. Infant expo sure was estimated as the product of actual or estimated milk producti on, and average drug concentration in milk, normalized to body weight and ex-pressed as a percentage of the weight-adjusted maternal dose. R esults Mean milk production was 321 ml day(-1) (range 34-974 ml). Mean M/P values of 1.93 and 1.64 were calculated for sertraline and N-desm ethylsertraline respectively. Infant exposure estimated from actual mi lk produced was 0.2% and 0.3% of the weight-adjusted maternal dose for sertraline and N-desmethylsertraline las sertraline equivalents) resp ectively. When calculated from estimated milk production (0.15 l kg(-1 ) day(-1)), infant exposure was significantly seater (P<0.0001) at 0.9 0% and 1.32% for sertraline and N-desmethylsertraline respectively. Ne ither sertraline nor its N-desmethyl metabolite could be detected in p lasma samples from the four infants tested. No adverse effects were ob served in any of the eight infants and all had achieved normal develop mental milestones. Conclusions Irrespective of the method of calculati on of infant exposure, the mean total dose of sertraline and its N-des methyl metabolite transmitted to infants via breast-feeding is low and unlikely to cause any significant adverse effects.