Excretion of Quetiapine 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.