Primidone and phenobarbital during lactation period in epileptic women: total and free drug serum levels in the nursed infants and their effects on neonatal behavior.

A total of 35 newborns whose mothers had been treated with either primidone (PMD), phenobarbital (PB) or a combination of one of these drugs with other antiepileptic drugs were included in this study. Fetal/maternal serum concentration ratios at birth, milk/serum concentration ratios and neonatal half-lives were determined for PMD, PB and phenylethylmalondiamide (PEMA). Steady-state serum levels of PMD in 2 nursed infants were 2.5 and 0.7 micrograms/ml, respectively, for PEMA values of 1.4 and 0.4 micrograms/ml. PB steady-state concentrations ranged between 2.0 and 13.0 micrograms/ml (6 infants). Maternal PB serum protein binding did not change during and after pregnancy. Neonatal free-fraction values at birth were similar to maternal values: 63.2 +/- 17.2% (n = 11). In the postnatal period, however, PB free-fraction values rose to more than 90% in some infants. In one case, neonatal free concentrations of PB were even higher during the 1st week after birth than the corresponding maternal values. Symptoms of sedation were observed in these neonates for which elevated free-fraction values of PB could be responsible. Behavior problems, such as withdrawal symptoms, were observed in neonates who eliminated PMD with short half-lives, while other infants with longer PMD half-lives or slower elimination because of nursing showed no such symptoms.