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Medline ® Abstract for Reference 51

of 'Safety of infant exposure to antidepressants and benzodiazepines through breastfeeding'

Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk.
Ilett KF, Hackett LP, Dusci LJ, Roberts MJ, Kristensen JH, Paech M, Groves A, Yapp P
Br J Clin Pharmacol. 1998;45(5):459.
AIMS: 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 (median100 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.
Department of Pharmacology, University of Western Australia, Nedlands.