Transfer of metformin into human milk.
Transfer of metformin into human milk.
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DOI：
10.1067/mcp.2003.9
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发表时间：
2003-01-01
影响因子：
6.7
通讯作者：
Saville, DJ
中科院分区：
文献类型：
--
作者：
Gardiner, SJ;Kirkpatrick, CMJ;Saville, DJ
目标。我们的目标是确定哺乳期母亲的乳汁与血浆中二甲双胍的比例并估计婴儿的暴露量。方法。进行了两项研究。在研究 1 中，对 3 名服用二甲双胍的哺乳母亲在稳态给药期间进行了研究。血液样本取自 2 名哺乳婴儿。在研究 2 中，5 名自愿在断奶后吸乳的健康哺乳期妇女在断奶时服用二甲双胍 500 毫克，并进行了长达 72 小时的研究。在这两项研究中，均估计了血浆和乳汁浓度-时间曲线下的面积，并根据浓度-时间曲线分析下的面积得出了乳汁与血浆的浓度比。通过标准方法计算婴儿剂量。结果。在研究 1 中，基于浓度-时间曲线分析下面积的乳汁与血浆浓度比分别为 0.37、0.50 和 0.71。根据体重进行调整后，母乳喂养的婴儿摄入的二甲双胍估计“剂量”分别为母体剂量的 0.18%、0.20% 和 0.21%。在母乳喂养的婴儿中，未检测到二甲双胍 (n = 2) 或注意到不良反应 (n = 3)。在研究 2 中，无法计算 3 名受试者基于浓度-时间曲线分析下面积的乳汁与血浆浓度比，因为二甲双胍在研究期结束后意外地在乳汁中持续存在。对于研究 72 小时的 2 名受试者，基于浓度-时间曲线分析下面积的乳汁与血浆浓度比分别为 0.27 和 0.47，婴儿剂量分别为 0.11% 和 0.25%。所有受试者牛奶中二甲双胍的浓度-时间曲线出乎意料地平坦。结论。由于婴儿接触量较低，二甲双胍在哺乳期间似乎是“安全的”。牛奶中二甲双胍不寻常的浓度-时间曲线表明二甲双胍转移到牛奶中并不完全依赖于被动扩散。
Objectives. Our objectives were to determine the milk-to-plasma ratio of metformin in lactating mothers and to estimate infant exposure.Methods. Two studies were performed. In study 1, 3 nursing mothers taking metformin were studied through-out a dosing interval at steady state. Blood samples were obtained from 2 suckling infants. In study 2, 5 healthy lactating women who volunteered to express milk after weaning were given metformin, 500 mg, at weaning and were studied for up to 72 hours. In both studies, areas under the plasma and milk concentration-time curves were estimated, and the milk-to-plasma concentration ratio based on area under the concentration-time curve analysis was derived. The infant dose was calculated by standard methods.Results. In study 1 the milk-to-plasma concentration ratios based on area under the concentration-time curve analysis were 0.37, 0.50, and 0.71. The estimated "doses" of metformin that would be ingested by the breast-fed infants were 0.18%, 0.20%, and 0.21% of the maternal doses, adjusted for weight. In the breast-fed infants, no metformin was detected (n = 2) or adverse effects noted (n = 3). In study 2, the milk-to-plasma concentration ratio based on area under the concentration-time curve analysis was unable to be calculated for 3 subjects because of the unexpected persistence of metformin in milk beyond the study period. For the 2 subjects studied for 72 hours, the milk-to-plasma concentration ratios based on area under the concentration-time curve analysis were 0.27 and 0.47 and the infant doses were 0.11% and 0.25%. The concentration-time profile for metformin in milk in all subjects was unexpectedly flat.Conclusions. Metformin appears to be "safe" during lactation because of low infant exposure. The unusual concentration-time profile for metformin in milk suggests that the transfer of metformin into milk is not solely dependent on passive diffusion.