Placental transfer to diazepam and its disposition in the newborn

Abstract

Diazepam (DZ) placental transfer in pregnant women at term, following single or repeated drug administration by various routes, was evaluated. DZ and its metabolite N-demethyldiazepam (NDZ) were constantly present in umbilical cord plasma at concentrations comparable to the mother's shortly after drug administration. N-methyloxazepam (MOX) was detected in cord plasma only in a limited number of cases following chronic DZ treatment. Postmortem analysis of fetal tissue concentrations showed accumulation of NDZ in heart and lungs. Differences in NDZ concentrations between venous cord (VC) and arterial cord (AC) plasms suggest metabolic degradation of DZ in the fetus. The DZ apparent plasma half-life in the newborn was found to be longer (31 plus or minus 2 hr) than previously observed in infants and children. The low drug clearance appears to be linked to reduced urinary excretion of hydroxylated metabolites, suggesting limited capability to dispose of DZ in the newborn.