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excretion of fluoxetine and norfluoxetine in human
Kristensen JH, Ilett KF, Hackett LP, Yapp P,
Paech M, Begg EJ.
Department of Pharmacy, King Edward
Memorial and Princess Margaret Hospitals, Subiaco, Western Australia.
AIMS: To characterize
milk/plasma (M/P) ratio and infant dose, for fluoxetine and
norfluoxetine, in breast-feeding women taking fluoxetine for the
treatment of depression, and to determine the plasma concentration of
these drugs 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-performance liquid
chromatography over a 24 h dose interval in four patients, and by single
point data collection in 10 patients. Infant exposure was estimated as
the product of estimated milk production, and average drug concentration
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 total infant exposure (fluoxetine
equivalents) was estimated to be 6.81% (range 2.15-12%) of the
weight-adjusted maternal dose of fluoxetine. Contributions from
fluoxetine and norfluoxetine were approximately equal. Fluoxetine (range
20-252 microgram l-1 ) was detected in five of the nine infants from
whom samples were collected, and norfluoxetine (range 17-187 microgram
l-1 ) was detected in seven of the nine infants. The highest of these
concentrations was about 70% of the maternal plasma concentrations.
CONCLUSIONS: The mean combined dose of fluoxetine and norfluoxetine
transmitted to infants via breast milk is below the 10% notional level
of concern. However, there was considerable interpatient variability in
estimated infant dose and in some of the patients, the dose was >10%.
Further, since adverse effects have been observed in breast-fed infants,
careful monitoring of the infants is mandatory. Neonates exposed to
these drugs in utero had higher concentrations of fluoxetine and
norfluoxetine and are at greater risk of adverse effects.
10583022 [PubMed - indexed for MEDLINE]