Paroxetine in human milk

Aims The primary aims of the study were to estimate the exposure of infants to paroxetine via breast milk and to determine the maternal milk:plasma ra tio (M/P) of paroxetine. Secondary aims were to compare single point and ar ea under the curve (AUC) estimates of M/P, to assess variability of M/P in fore and hind milk, and to compare the observed M/P with that predicted by a model. Methods Two studies were performed. In one study, six nursing mothers who w ere being treated with paroxetine were studied over a 24 h dose interval at steady-state. The total amount of paroxetine in the milk was measured, whi ch represented the 'dose' to the infant. The M/P-AUC was calculated and com pared with a predicted value. In the second study, four nursing mothers who were being treated with paroxetine, were studied at steady-state, around a normal infant feeding time. A single plasma sample and a prefeed milk samp le were taken approximately 3 h after the morning dose of paroxetine, and a postfeed milk sample taken around 1 h later. The dose received by the infa nt was estimated from the average milk concentrations of the pre and postfe ed samples using standard assumptions, and M/P calculated directly. Plasma concentrations of paroxetine were measured in 8 of the 10 infants in the tw o studies. Results The mean dose of paroxetine received by the infants in the first st udy was 1.13% (range 0.5-1.7) of the weight adjusted maternal dose. The mea n M/P-AUC was 0.39 (range 0.32-0.51). The predicted M/P was 0.22. The mean dose of paroxetine received by the infants in the second study was 1.25% (r ange 0.38-2.24) of the weight adjusted maternal dose. The mean M/P was 0.96 (range 0.31-3.33) and did not differ between fore and hind milk. The drug was not detected in the plasma of seven of the infants studied and was dete cted but not quantifiable (<4 mu g1(-1)) in one infant. No adverse effects were observed in any of the infants. Conclusions Measured M/P and estimated infant dose were similar in the two studies, although the range was wider for the single point study. Paroxetin e can be considered 'safe' during breast feeding because the dose transferr ed to the infant is well below the recommended safety limit of 10% of the w eight adjusted maternal dose, concentrations in the infants were generally undetectable, and no adverse effects were reported.