title: Transfer of olanzapine into breast milk, calculation of infant drug dose, and effect on breast-fed infants.
abstract: OBJECTIVE
  This study characterized infant drug doses and breast-milk-to-plasma area-under-the-curve ratios for olanzapine and determined plasma concentrations and effects of this drug on breast-feeding infants.
  
  
  METHODS
  Seven mother-infant nursing pairs were studied. Olanzapine was measured in plasma and milk with high-performance liquid chromatography over a dose interval (for six patients) or at a single time after dose ingestion (for one patient) at steady state. Infant drug exposure was estimated as the product of an assumed milk production rate and average drug concentration in milk, normalized to body weight, and expressed as a percentage of maternal drug dose, normalized to body weight.
  
  
  RESULTS
  The median infant dose of olanzapine ingested through milk was 1.02% of the maternal dose; the median milk-to-plasma area-under-the-curve ratio was 0.38 for the six patients with data collected over the dose interval. Corresponding values in the patient with single-point data were 1.13% and 0.75. Olanzapine was not detected in the plasma of the six infants with an evaluable plasma sample. All of the infants were healthy and experienced no side effects.
  
  
  CONCLUSIONS
  Breast-fed infants were exposed to a calculated olanzapine dose of approximately 1%-well below the 10% notional level of concern. In infant plasma, olanzapine was below the detection limit; there were no adverse effects on the infants. These data support the use of olanzapine during breast-feeding. However, the authors recommend that breast-fed infants be monitored closely and the decision to breast-feed be made after individual risk-benefit analysis.
authors.affiliation: Department of Clinical Pharmacology, Christchurh Hospital, New Zealand. sharon.gardiner@cdhb.govt.nz
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Gardiner
authors.forename: Judith H
authors.initials: JH
authors.lastname: Kristensen
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Begg
authors.forename: L Peter
authors.initials: LP
authors.lastname: Hackett
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Wilson
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Ilett
authors.forename: Rolland
authors.initials: R
authors.lastname: Kohan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rampono
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001569:Benzodiazepines; D001942:Breast Feeding; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008895:Milk, Human / Q000737:chemistry / Q000378:metabolism*; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine