title: Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk.
abstract: OBJECTIVE
  To characterise the transfer of venlafaxine (V) and its O-desmethyl metabolite (ODV) into human milk by measuring milk/plasma (M/P) ratio, and to estimate the likely dose received by a breast-fed infant.
  
  
  METHODS
  Milk and plasma samples were collected from three lactating women who were taking venlafaxine for depression, and were at steady-state. In two of the patients, venous blood and milk samples were collected 0, 1, 2, 3, 4, 6, 8 and 12 h post dose, while in the third patient a single pair of blood and milk samples was obtained 0.83 h post dose. A plasma sample was obtained from each of their infants. V and ODV were measured in plasma and milk by high performance liquid chromatography. M/P was calculated and infant dose estimated as drug concentration in milk x a milk intake of 0.15 l kg(-1) day(-1), relative to the weight-adjusted maternal dose.
  
  
  RESULTS
  Mean M/P for V was 4.1 (range 2.8-4.8) and 3.1 for ODV (range 2.8-3.8). The mean total infant dose (as V equivalents) was 7.6% (range 4.7-9.2%) of the maternal weight-adjusted dose, with approximately equal amounts of V (3.5%) and ODV (4.1%) in the dose. ODV (median 100 microg I(-1)) was detected in the plasma of all three infants. The infants were healthy and showed no acute adverse effects.
  
  
  CONCLUSIONS
  These preliminary data show that the total dose of V and ODV ingested by breast-fed infants can be as high as 9.2% of maternal intake. Moreover there were measurable concentrations of ODV in the infants' plasma. We recommend that exposed infants should be observed closely.
authors.affiliation: Department of Pharmacology, University of Western Australia, Nedlands.
authors.forename: K F
authors.initials: KF
authors.lastname: Ilett
authors.forename: L P
authors.initials: LP
authors.lastname: Hackett
authors.forename: L J
authors.initials: LJ
authors.lastname: Dusci
authors.forename: M J
authors.initials: MJ
authors.lastname: Roberts
authors.forename: J H
authors.initials: JH
authors.lastname: Kristensen
authors.forename: M
authors.initials: M
authors.lastname: Paech
authors.forename: A
authors.initials: A
authors.lastname: Groves
authors.forename: P
authors.initials: P
authors.lastname: Yapp
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000032:analysis / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001942:Breast Feeding; D002851:Chromatography, High Pressure Liquid; D003511:Cyclohexanols / Q000032:analysis / Q000493:pharmacokinetics*; D000069468:Desvenlafaxine Succinate; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008895:Milk, Human / Q000737:chemistry* / Q000378:metabolism; D014018:Tissue Distribution; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride; D000069468:Desvenlafaxine Succinate