産後早期の母体、初乳、母乳栄養新生児におけるラモトリギン濃度のモニタリング

Monitoring of lamotrigine concentrations in mothers, colostrum, and breastfed newborns during the early postpartum period.

抄録

目的:

母体血清，初乳および母乳栄養新生児の血清中のラモトリギン濃度を解析し，酵素誘導型抗けいれん薬およびバルプロ酸の併用効果を評価する。

OBJECTIVE: 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.

方法:

このコホート研究は、158人の女性と143人の母乳育児新生児のデータを収集した。母体血清、乳汁（初乳）、新生児血清のサンプルを生後2日から5日の間に採取し、ラモトリギン濃度を高速液体クロマトグラフィーで測定した。

METHODS: 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.

結果:

ラモトリギン濃度の中央値は、母体血清で2.7mg/L、乳汁で1.4mg/L、新生児血清で1.7mg/Lであった。乳汁/母体血清濃度比の中央値は0.60、新生児/母体血清濃度比の中央値も0.60、新生児血清/乳汁濃度比の中央値は1.00であった。乳汁と母体血清の濃度，新生児血清と乳汁の濃度，母体血清の濃度，母体の1日投与量，母体体重に関連する投与量の間に有意な相関が認められた．

RESULTS: 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.

結論:

母乳栄養の新生児におけるラモトリジンの曝露量は、妊娠中の曝露量より低い。しかし，同一母体による同一用量では，出産後に母体血清および乳汁中のラモトリギン濃度は有意に上昇する．この所見は、新生児の排泄酵素の機能が未熟であることと合わせて、母乳栄養新生児において一般てんかん患者群に用いられる基準範囲内の濃度に達する理由であると思われる。母乳栄養新生児のラモトリギン血清濃度の治療的モニタリングは必須ではありませんが、有害事象の可能性が指摘された場合には、新生児の血清濃度を分析する必要があります。

CONCLUSIONS: 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.