Distribution and excretion of fluoxetine and norfluoxetine in human milk

Aims To characterize milk/plasma (M/P) ratio and infant dose, for fluoxetin e and norfluoxetine, in breast-feeding women taking fluoxetine for the trea tment of depression, and to determine the plasma concentration of these dru gs in their infants. Methods Fourteen women (mean age 32.2 years) taking fluoxetine (mean dose 0 .51 mg kg(-1) day(-1)) and their infants (mean age 3.4 months) were studied . Fluoxetine and norfluoxetine in plasma and milk were measured by high-per formance liquid chromatography over a 24 h dose interval in four patients, and by single point data collection in 10 patients. Infant exposure was est imated as the product of estimated milk production, and average drug concen tration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. Results Mean M/P values of 0.68 (95% CI 0.52-0.84) and 0.56 (95% CI 0.35-0. 77) were calculated for fluoxetine and norfluoxetine, respectively. Mean to tal infant exposure (fluoxetine equivalents) was estimated to be 6.81% (ran ge 2.15-12%) of the weight-adjusted maternal dose of fluoxetine. Contributi ons from fluoxetine and norfluoxetine were approximately equal. Fluoxetine (range 20-252 mu g l(-1)) was detected in five of the nine infants from who m samples were collected, and norfluoxetine (range 17-187 mu g l(-1)) was d etected in seven of the nine infants. The highest of these concentrations w as about 70% of the maternal plasma concentrations. Conclusions The mean combined dose of fluoxetine and norfluoxetine transmit ted to infants via breast milk is below the 10% notional level of concern. However, there was considerable interpatient variability in estimated infan t dose and in some of the patients, the dose was >10%. Further, since adver se effects have been observed in breast-fed infants, careful monitoring of the infants is mandatory. Neonates exposed to these drugs in utero had high er concentrations of fluoxetine and norfluoxetine and are at greater risk o f adverse effects.