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

Abstract

In six full-term newborn infants born to epileptic mothers, the cord-to-maternal concentration ratios of anticonvulsants and the plasma disappearance of the drugs transferred across the placenta were studied. The respective mean +/- SEM values for the ratio of the cord-to-maternal blood concentration were: 0.95 +/- 0.05 (n = 5) for phenobarbital (PB), 0.97 +/- 0.04 (n = 3) for phenytoin (PHT), and 1.71 +/- 0.23 (n = 4) for valproic acid (VPA). The disappearance from the plasma of neonates showed a discernible two-component (initially slow and then fast) curve for all cases with PB, for one with PHT, and for two with VPA. Half-lives calculated from the terminal elimination phase were: 74.0 +/- 8.8 hours for PB (n = 5) and 26.8 +/- 4.8 hours (n = 4) for VPA. The half-life value of PB observed in this study 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 shorter than that from a neonate in the literature.