Johannessen S I
National Centre for Epilepsy, Sandvika, Norway.
Pharm Weekbl Sci. 1992 Jun 19;14(3A):114-7. doi: 10.1007/BF01962699.
An increased risk of seizures during and immediately after labour has been observed in epileptic women, and it is recognized that serum levels of antiepileptic drugs may decrease in pregnancy. Several studies have suggested that total valproate levels fall, but that free fractions increase during pregnancy. Recent findings suggest that the actual metabolism of valproate is not altered by pregnancy and that the changes of the plasma clearance are due primarily to decreased protein binding. The levels of free drug will not change significantly as pregnancy advances. However, dose reduction after delivery may be necessary to avoid toxicity. Valproate and its metabolites undergo placental transfer. In the foetus the plasma level of valproate and the protein binding are higher than in maternal plasma, and the half-life of valproate following placental transfer is considerably longer than in adults. Only small amounts of valproate appear in breast milk and those are not likely to cause any problems. During pregnancy and the first month after delivery preferably both total and free valproate serum levels should be closely monitored to determine the lowest effective dose.
已观察到癫痫女性在分娩期间及分娩后即刻癫痫发作风险增加，并且人们认识到孕期抗癫痫药物的血清水平可能会降低。多项研究表明，丙戊酸盐的总水平下降，但孕期游离部分增加。最近的研究结果表明，丙戊酸盐的实际代谢并未因怀孕而改变，血浆清除率的变化主要是由于蛋白质结合减少。随着孕期进展，游离药物水平不会有显著变化。然而，产后可能需要减少剂量以避免毒性。丙戊酸盐及其代谢产物会发生胎盘转运。在胎儿体内，丙戊酸盐的血浆水平和蛋白质结合率高于母体血浆，胎盘转运后丙戊酸盐的半衰期比成年人长得多。母乳中仅含有少量丙戊酸盐，不太可能引起任何问题。在孕期及产后第一个月，最好密切监测丙戊酸盐的血清总水平和游离水平，以确定最低有效剂量。
