To the Editor: To our knowledge, there is no published report regarding the excretion of the antipsychotic agent quetiapine into breast milk. In this case report, we describe what we think is the first account of measuring quetiapine levels in breast milk.
Ms. A, a 36-year-old woman (92.5 kg, gravida one, para one), contacted our program after the birth of a full-term male infant. She was taking 200 mg/day of quetiapine throughout pregnancy and wished to continue treatment and to breast-feed her infant. Because no previous measurements on the excretion of quetiapine in breast milk existed in the published literature, Ms. A and her physician decided to feed the infant formula until breast-milk measurements were available. Written informed consent was obtained from Mr. A after the procedures had been fully explained.
Manually expressed breast-milk samples were collected over a 6-hour period at 3 weeks postpartum. Samples were obtained just before quetiapine dosing and again at 1, 2, 4, and 6 hours postdose. Samples were kept frozen at –20°C until analysis. The breast-milk samples were centrifuged at 8,000 rpm. The infranatant was extracted with heptane/isoamyl alcohol (98.5/1.5) at alkaline pH. The solvent extract was dried off and reconstituted with phosphate buffer (pH=2.5), and the solution was washed twice with heptane. High-performance liquid chromatography analysis was performed by using 150 mm of C18 column Kromasil (Chromomatography Sciences Company, Inc., Montreal). The mobile phase consisted of a phosphate buffer (pH=2.5) containing acetonitrile (25% vol/vol) and methanol (19% vol/vol). Quetiapine was measured by using photodiode array detection, and the linear calibration curve ranged from 2–500 μg/liter.
The area under the curve of quetiapine in breast milk from time 0 to 6 hours was calculated by using the trapezoidal method. The elimination half-life of quetiapine in breast milk was calculated by using the log-linear elimination phase of the drug. The daily amount of quetiapine ingested by a nursing infant was calculated by assuming that an infant ingests 150 ml/kg/day of breast milk and by using the average milk concentration of quetiapine over 6 hours. The maximum amount an infant will ingest was calculated based on the highest milk concentration.
The average milk concentration of quetiapine over the 6 hours was 13 μg/liter, with a maximum concentration of 62 μg/liter at 1 hour. Levels of quetiapine rapidly fell to almost predose levels by 2 hours. Therefore, an exclusively breast-fed infant would ingest only 0.09% of the weight-adjusted maternal dose. At maximum, the infant would ingest 0.43% of the weight-adjusted maternal dose.
Upon receiving the results of levels in the breast milk, the woman began breast-feeding exclusively at 8 weeks after delivery. Follow-up of the infant at 4.5 months indicated that the infant was developing well, and no adverse effects of quetiapine were reported.
Although more studies are required to confirm our findings, the level of infant exposure to quetiapine in breast milk appears to be too small for significant pharmacological effects.