Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic; Department of Clinical Pharmacology, Department of Laboratory Diagnostics, University Hospital Ostrava, 17. listopadu 1790/5, 708 52 Ostrava, Czech Republic.
Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic.
Epilepsy Behav. 2019 Jun;95:112-116. doi: 10.1016/j.yebeh.2019.04.002. Epub 2019 Apr 28.
Valproic acid (VPA) is currently one of the four most often prescribed antiepileptic drugs (AEDs) in pregnancy. However, only a small number of studies have measured suckling infant serum levels of the drug. We studied the transport of VPA from breastfeeding mothers to the mature milk and breastfed infants and the influence of comedication with enzyme-inducing AEDs. The data of 30 nursing women treated by VPA were analyzed retrospectively. Mature milk, maternal, and infant serum levels were collected between the 6th and 32nd postnatal day and measured by gas chromatography during the years 1996-2017. Valproic acid levels varied from 5.4 to 69.0 mg/L (mean: 39.0 ± 16.1 mg/L) in the maternal serum, from <1.0 to 16.7 mg/L (mean: 1.6 ± 3.9 mg/L) in the milk, and from <1.0 to 17.5 mg/L (mean: 4.2 ± 4.3 mg/L) in the infant serum. The milk/maternal serum level ratio ranged from <0.03 to 0.25 (mean: 0.03 ± 0.06) and the infant/maternal serum level ratio from <0.03 to 0.61 (mean: 0.11 ± 0.13). Sixty-seven percent of milk and 33% of infant VPA concentrations were below the limit of quantification. No correlations were observed between maternal serum and milk levels or between maternal and infant serum levels. In conclusion, none of the milk or infant serum VPA levels reached the lower limit of the reference range used for the general population with epilepsy, so the degree of VPA exposure in breastfed infants is less than during gestation. Nevertheless, if signs of potential adverse reactions manifest, infant serum concentrations should be measured.
丙戊酸（VPA）目前是妊娠期间最常开的四种抗癫痫药物（AEDs）之一。然而，只有少数研究测量了哺乳婴儿的血清药物水平。我们研究了 VPA 从哺乳母亲转移到成熟乳汁和母乳喂养婴儿的情况，以及与酶诱导性 AED 联合用药的影响。我们回顾性分析了 30 名接受 VPA 治疗的哺乳期妇女的数据。在 1996 年至 2017 年期间，收集了产后第 6 天至第 32 天的成熟乳、产妇和婴儿血清样本，并通过气相色谱法进行了测量。产妇血清中的 VPA 水平为 5.4 至 69.0mg/L（平均值：39.0±16.1mg/L），乳汁中为 <1.0 至 16.7mg/L（平均值：1.6±3.9mg/L），婴儿血清中为 <1.0 至 17.5mg/L（平均值：4.2±4.3mg/L）。乳汁/母血清水平比值范围为 <0.03 至 0.25（平均值：0.03±0.06），婴儿/母血清水平比值范围为 <0.03 至 0.61（平均值：0.11±0.13）。67%的乳汁和 33%的婴儿 VPA 浓度低于定量下限。母血清与乳汁水平之间或母血清与婴儿血清水平之间均未观察到相关性。总之，母乳喂养婴儿的乳汁或婴儿血清 VPA 水平均未达到用于普通癫痫人群的参考范围下限，因此婴儿暴露于 VPA 的程度小于妊娠期间。尽管如此，如果出现潜在不良反应的迹象，应测量婴儿血清浓度。
