Placental transfer and pharmacokinetics of primidone and its metabolites phenobarbital, PEMA and hydroxyphenobarbital in neonates and infants of epileptic mothers

Abstract

The placental transfer of primidone and its metabolites phenobarbital, phenylethylmalondiamide (PEMA) and p-hydroxyphenobarbital (free and conjugated) has been investigated at birth in 14 epileptic women who had been treated with primidone throughout pregnancy. All drugs studied were found in similar concentrations in maternal and cord blood. In seven of the newborns the pharmacokinetics of these drugs were studied during the first postnatal weeks. Primidone and phenobarbital were eliminated with mean half-lives of 23±10 h and 113±40 h, respectively, PEMA with 35±6 h. In some neonates the serum concentrations of phenobarbital and PEMA increased during the first few days due to their formation by neonatal primidone metabolism. Some babies showed a biphasic elimination pattern with elimination rates increasing after a few days. Although half-lives varied greatly, they corresponded well with renal clearance values and aminopyrine demethylase activities as measured by13CO2-exhalation from13C-labelled aminopyrine. Two newborns whose mothers had been treated with phenytoin in addition to primidone, showed half-lives, renal clearance values and aminopyrine demethylase activities well within the corresponding ranges for adults, thus demonstrating prenatal induction. Newborns whose mothers had been treated with valproate as comedication, did not exhibit elevated excretion rates as compared to newborns of mothers who were treated with primidone alone. Withdrawal symptoms developed in two newborns at times when primidone had been essentially excreted, and in spite of the presence of elevated phenobarbital and PEMA levels. All drugs studied were also present in mothers' milk. During breast feeding, drugs ingested with the milk contributed to the neonate's blood levels, particularly in the case of phenobarbital.

DOI: 10.1007/BF00561476

7 Figures and Tables

Statistics

050100150'82'85'89'93'97'01'05'09'13'17
Citations per Year

233 Citations

Semantic Scholar estimates that this publication has 233 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Nau1980PlacentalTA, title={Placental transfer and pharmacokinetics of primidone and its metabolites phenobarbital, PEMA and hydroxyphenobarbital in neonates and infants of epileptic mothers}, author={H. E. Nau and Dielz Rating and Ivan H{\"a}user and Elke Jaeger and Sandra N Koch and Hans Helge}, journal={European Journal of Clinical Pharmacology}, year={1980}, volume={18}, pages={31-42} }