Pharmacokinetics of duloxetine in breast milk and plasma of healthy postpartum women.
OBJECTIVE
The purpose of this study was to characterize duloxetine pharmacokinetics in the breast milk and plasma of lactating women and to estimate the duloxetine dose that an infant might consume if breastfed.


METHODS
This open-label study included six healthy women aged 22-35 years who stopped nursing during and after the study. Duloxetine 40 mg was given orally every 12 hours for 3.5 days; seven plasma and milk samples over 12 hours were obtained after the seventh dose. Plasma and milk samples were analysed using validated liquid chromatography-tandem mass spectrometry methods. Safety measures included vital signs, ECGs, laboratory tests, adverse event monitoring and depression rating scales.


RESULTS
The mean steady-state milk-to-plasma duloxetine exposure ratio was 0.25 (90% CI 0.18, 0.35). The amount of duloxetine in the breast milk was 7 microg/day (range 4-15 microg/day). The estimated infant dose was 2 microg/kg/day (range 0.6-3 microg/kg/day), which is 0.14% of the maternal dose. Dizziness, nausea and fatigue were commonly reported adverse events. No clinically important changes in safety measures occurred.


CONCLUSIONS
Duloxetine is detected in breast milk, and steady-state concentrations in breast milk are about one-fourth of those in maternal plasma. As the safety of duloxetine in infants is unknown, prescribers should carefully assess, on an individual basis, the potential risks of duloxetine exposure to infants and the benefits of nursing an infant when the mother is on duloxetine therapy.
Lobo
Evelyn D
ED
Eli Lilly and Company, Indianapolis, Indiana 46285-0724, USA. loboev@lilly.com
Loghin
Corina
C
Knadler
Mary Pat
MP
Quinlan
Tonya
T
Zhang
Lu
L
Chappell
Jill
J
Lucas
Richard
R
Bergstrom
Richard F
RF
D000284:Administration, Oral; D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D002214:Capsules; D002853:Chromatography, Liquid; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006261:Headache / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007774:Lactation / Q000097:blood / Q000378:metabolism; D008895:Milk, Human / Q000378:metabolism*; D009325:Nausea / Q000139:chemically induced; D049590:Postpartum Period / Q000097:blood / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry; D013876:Thiophenes / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
D002214:Capsules; D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes