Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic; Department of Clinical Pharmacology, Institute of Laboratory Medicine, University Hospital Ostrava, 17. listopadu 1790, 700 30 Ostrava, Czech Republic.
Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic; Department of Clinical Pharmacology, Institute of Laboratory Medicine, University Hospital Ostrava, 17. listopadu 1790, 700 30 Ostrava, Czech Republic.
Biomed Pharmacother. 2022 Jul;151:113167. doi: 10.1016/j.biopha.2022.113167. Epub 2022 May 24.
To analyse the concentrations of lamotrigine in maternal serum, colostrum, and serum of breastfed newborns, and to evaluate the effect of comedication with enzyme-inducing antiseizure medication and valproic acid.
This cohort study collected data from 158 women and 143 breastfed newborns. Maternal serum, milk (i.e., colostrum), and newborn serum samples were collected between the 2nd and 5th postnatal days, and lamotrigine concentrations were measured by high-performance liquid chromatography.
The median lamotrigine concentrations were 2.7 mg/L in maternal serum, 1.4 mg/L in milk, and 1.7 mg/L in newborn serum. The median milk/maternal serum concentration ratio was 0.60, the median newborn/maternal serum concentration ratio was also 0.60, and the median newborn serum/milk concentration ratio was 1.00. A significant correlation was observed between milk and maternal serum concentrations and between newborn serum and milk concentrations, maternal serum concentrations, maternal daily dose, and dose related to maternal body weight.
Exposure to lamotrigine in breastfed newborns is lower than exposure during pregnancy. However, by the same dose by the same mother, lamotrigine concentrations in both maternal serum and milk increase significantly after delivery. This finding, together with the immature function of eliminating enzymes in newborns, may be the reason for reaching concentrations in the reference range used for the general epileptic population in breastfed newborns. Therapeutic monitoring of breastfed newborns serum concentrations of lamotrigine is not mandatory; however, if signs of possible adverse events are noted, newborn serum concentrations should be analysed.
分析母血清、初乳和母乳喂养新生儿血清中拉莫三嗪的浓度,并评估合并使用酶诱导抗癫痫药物和丙戊酸的效果。
这项队列研究收集了 158 名女性和 143 名母乳喂养新生儿的数据。在产后第 2 至第 5 天采集母血清、乳汁(即初乳)和新生儿血清样本,并通过高效液相色谱法测定拉莫三嗪浓度。
母血清中拉莫三嗪的中位数浓度为 2.7mg/L,乳中为 1.4mg/L,新生儿血清中为 1.7mg/L。乳汁/母血清浓度比值的中位数为 0.60,新生儿/母血清浓度比值也为 0.60,新生儿血清/乳浓度比值为 1.00。乳与母血清浓度之间以及新生儿血清与乳、母血清浓度之间存在显著相关性,与母每日剂量以及与母体体重相关的剂量有关。
母乳喂养的新生儿接触拉莫三嗪的量低于妊娠期间。然而,由同一母亲给予相同剂量,产后母血清和乳中的拉莫三嗪浓度显著增加。这一发现,加上新生儿消除酶功能不成熟,可能是母乳喂养的新生儿达到一般癫痫人群所用参考范围浓度的原因。对母乳喂养的新生儿进行拉莫三嗪血清浓度的治疗性监测并非强制性的;然而,如果出现可能的不良反应迹象,应分析新生儿血清浓度。