Alexianer Hospital Aachen, Aachen, Germany.
Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074, Aachen, Germany.
Clin Pharmacokinet. 2019 Apr;58(4):535-543. doi: 10.1007/s40262-018-0713-y.
The aim of this study was to measure and investigate correlations of lamotrigine concentrations in maternal as well as umbilical cord blood, amniotic fluid, and breast milk to account for the distribution of the drug.
Concentrations of lamotrigine were measured in 19 mother-infant pairs at the time of delivery. To account for the penetration ratio into amniotic fluid, cord blood and breast milk, the concentration of lamotrigine in the particular environment was divided by the concentration in maternal serum. A no-intercept model was applied for associations between maternal serum concentrations, amniotic fluid, umbilical cord blood, and breast milk concentrations.
The mean daily dosage of lamotrigine was 351.32 mg (range 50-650 mg). We detected associations between maternal serum and amniotic fluid (β = 0.088, p < 0.001), as well as umbilical cord (β = 0.939, p < 0.001) and breast milk (β = 0.964, p < 0.001). The median penetration ratio into amniotic fluid, cord blood, and breast milk was 0.68, 0.92, and 0.77, respectively.
Lamotrigine concentrations in amniotic fluid, cord blood, and breast milk give evidence that the fetus/newborn is constantly exposed to lamotrigine. Maternal serum concentrations predicted exposure via amniotic fluid, umbilical cord, and breast milk. Data suggest that therapeutic drug monitoring can be recommended as part of the clinical routine in psychopharmacotherapy for pregnant or breastfeeding women.
本研究旨在测量和研究拉莫三嗪在产妇及脐带血、羊水和母乳中的浓度,以了解药物的分布情况。
在分娩时,对 19 对母婴进行了拉莫三嗪浓度的测量。为了计算药物进入羊水、脐带血和母乳的渗透比率,将特定环境中的拉莫三嗪浓度除以母血清中的浓度。采用无截距模型来关联母血清浓度、羊水、脐带血和母乳浓度。
拉莫三嗪的平均日剂量为 351.32mg(范围 50-650mg)。我们发现母血清与羊水(β=0.088,p<0.001)、脐带(β=0.939,p<0.001)和母乳(β=0.964,p<0.001)之间存在关联。进入羊水、脐带血和母乳的中位数渗透比率分别为 0.68、0.92 和 0.77。
羊水、脐带血和母乳中的拉莫三嗪浓度表明胎儿/新生儿不断暴露于拉莫三嗪中。母血清浓度可通过羊水、脐带和母乳预测暴露情况。数据表明,治疗药物监测可以作为孕妇或哺乳期妇女精神药理学治疗的临床常规的一部分进行推荐。