DISTRIBUTION AND EXCRETION OF VENLAFAXINE AND O-DESMETHYLVENLAFAXINE IN HUMAN-MILK

Aims To characterise the transfer of venlafaxine (V) and its O-desmeth yl metabolite (ODV) into human milk by measuring milk/plasma (M/P) rat io, and to estimate the likely dose received by a breast-fed infant. M ethods Milk and plasma samples were collected from three lactating wom en who were taking venlafaxine for depression, and were at steady-stat e, In two of the patients, venous blood and milk samples were collecte d 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 wer e measured in plasma and milk by high performance Liquid chromatograph y. 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 weig ht-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 las 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 mu g l(-1)) was detected in the plasma of al l three infants. The infants were healthy and showed no acute adverse effects. Conclusions These preliminary data show that the total dose o f V and ODV ingested by breast-fed infants can be as high as 9.2% of m aternal intake. Moreover there were measurable concentrations of ODV i n the infants' plasma. We recommend that exposed infants should be obs erved closely.