Ilett K F, Hackett L P, Dusci L J, Roberts M J, Kristensen J H, Paech M, Groves A, Yapp P
Department of Pharmacology, University of Western Australia, Nedlands.
Br J Clin Pharmacol. 1998 May;45(5):459-62. doi: 10.1046/j.1365-2125.1998.00710.x.
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.
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.
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.
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.
通过测量乳汁/血浆（M/P）比值来描述文拉法辛（V）及其O-去甲基代谢物（ODV）向人乳中的转运情况，并估算母乳喂养婴儿可能摄入的剂量。
从三名因抑郁症服用文拉法辛且处于稳态的哺乳期妇女中采集乳汁和血浆样本。其中两名患者在给药后0、1、2、3、4、6、8和12小时采集静脉血和乳汁样本，第三名患者在给药后0.83小时采集一对血样和乳汁样本。从她们的每个婴儿中采集一份血浆样本。采用高效液相色谱法测定血浆和乳汁中的V和ODV。计算M/P比值，并将婴儿剂量估算为乳汁中的药物浓度×0.15 l kg⁻¹天⁻¹的乳汁摄入量，相对于体重调整后的母亲剂量。
V的平均M/P比值为4.1（范围2.8 - 4.8），ODV为3.1（范围2.8 - 3.8）。婴儿的平均总剂量（以V等效物计）为母亲体重调整剂量的7.6%（范围4.7 - 9.2%），剂量中V（3.5%）和ODV（4.1%）的量大致相等。在所有三名婴儿的血浆中均检测到ODV（中位数100 μg l⁻¹）。婴儿健康，未出现急性不良反应。
这些初步数据表明，母乳喂养婴儿摄入的V和ODV总剂量可高达母亲摄入量的9.2%。此外，婴儿血浆中ODV的浓度可测。我们建议对暴露的婴儿应密切观察。
