Anticonvulsants during Pregnancy and Lactation Transplacental, Maternal and Neonatal Pharmacokinetics

  title={Anticonvulsants during Pregnancy and Lactation Transplacental, Maternal and Neonatal Pharmacokinetics},
  author={Heinz Nau and Wilhelm Kuhnz and H J Egger and Dietz Rating and Hans Helge},
  journal={Clinical Pharmacokinetics},
SummaryFew data are available on placental transfer of anticonvulsants during early pregnancy. Nevertheless, it has been demonstrated that at this early stage of gestation, considerable amounts of Phenytoin, primidone/phenobarbitone and carbamazepine as well as some of their metabolites are already present in fetal tissues. Potentially reactive metabolites of anticonvulsants can be formed by the fetal liver and accumulate in some organs. At term, most anticonvulsants are present in neonatal… 

Pharmacokinetics of valproate in pregnancy: Mother-foetus-newborn

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.

Antiepileptic drug pharmacokinetics during pregnancy and lactation

Future studies of formal pharmacokinetic modeling of AEDs during pregnancy and the postpartum period could provide an important step toward achieving effective drug dosing to maintain therapeutic objectives for the mother but, at the same time, to minimize fetal drug exposure.

Farmacología del feto y el recién nacido

Considering the physicochemical properties of the substances, the possibility of such compounds to cross the placenta barrier and thence to the fetus can be predicted and the advantages and disadvantages of the use of such drugs for the care of a being yet in development are considered.

Ethosuximide in epileptic women during pregnancy and lactation period. Placental transfer, serum concentrations in nursed infants and clinical status.

A total of 10 epileptic mothers treated with ethosuximide as well as their 13 newborns were included in this study and two major malformations were observed in two neonates whose mothers received either ES/PB or ES/PMD comedication.

Concerns regarding lamotrigine and breast-feeding

Psychotropic Drugs in Pregnancy and Lactation

There would appear to be an increased risk for spontaneous malformations in the case of lithium and there have been inconsistent reports of structural abnormalities following exposure to phenothiazines and benzodiazepines.

Drug disposition in the maternal-fetal unit : studies with diphenhydramine and valproic acid in pregnant sheep

Maternal and fetal placental and non-placental clearances of both drugs were highly dependent on their plasma protein binding, but for DPHM, the importance of plasmaprotein binding in determining fetal drug exposure was overridden by the above more pronounced effect of the fetal liver.

The use of anticonvulsants during pregnancy.

  • M. Yerby
  • Medicine
    Seminars in perinatology
  • 2001
The exclusion of women of childbearing age from clinical trials limits the ability to collect information on the pharmacokinetics and potential adverse experiences of AED in pregnancy, and the current understanding of the use of A ED in women ofChildbearing age is described.

Anticonvulsant Use During Lactation

The issue of prescribing anticonvulsant drugs during lactation is clinically important, but also complex and no clearcut recommendations can be made until further data are present.



Placental transfer of anticonvulsants (phenobarbital, phenytoin, valproic acid) and the elimination from neonates.

The half-life value of PB was found to be shorter than that observed postnatally in the previous reports, while that of VPA was two to three times as long as that reported from children or adults, but short than that from a neonate in the literature.

Valproic acid and its metabolites: placental transfer, neonatal pharmacokinetics, transfer via mother's milk and clinical status in neonates of epileptic mothers.

The pharmacokinetics of valproic acid (VPA) and several metabolites were measured in 11 epileptic mothers and their 12 newborns and the very low levels of VPA in mother's milk suggest apparent safety of breast feeding.


Preliminary data suggest that primidone intake during pregnancy may be important in the pathogenesis of minor anomalies and in the induction of poor somatic development.

Phenytoin Metabolism in Pregnancy

Pregnancy is associated with altered DPH absorption or metabolism, or both, and periodic measurement of plasma DPH concentration is valuable when managing a pregnant epileptic patient, the authors conclude.

Transplacental passage of primidone

A neurologic syndrome of abnormal tremulousness in a newborn infant whose mother had received primidone during pregnancy is observed, and it is presented here a report of this case.

Placental transfer and neonatal elimination of diphenylhydantoin.

  • B. Mirkin
  • Medicine
    American journal of obstetrics and gynecology
  • 1971

Clinical Pharmacokinetics in Neonates

It is clearly emerging that drug disposition may vary greatly in the newborn in relation to its developmental age, and the significance of various factors on drug dispostion during development will be better clarified, thus allowing a more rational and safer therapy inThe newborn.

Urinary corticosteriod and diphenylhydantoin metabolite patterns in neonates exposed to anticonvulsant drugs in utero

The enhanced 6β‐hydroxylation of cortisol seen in adults after barbiturate or diphenylhydantoin was not observed in newborns exposed to these drugs in utero.