Distribution and excretion of venlafaxine and O‐desmethylvenlafaxine in human milk

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Abstract
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×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 μg l−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.