Time-course of Transplacental Passage of Diazepam

Abstract

Neonatal drug concentrations and neonate/mother concentration ratios are reported in 73 cases of elective Caesarean section and forceps deliveries where diazepam was used as an intravenous sleep-inducing agent. The various parameters were plotted against the injection-delivery interval and the correlation was tested using a non-parametric ranking method. The concentration of diazepam in mixed arteriovenous umbilical cord blood was negatively correlated with the injection-delivery interval in the range of 55 to 810 seconds. Statistically significant positive correlation (p less than 0.001) were found between the injection-delivery interval and the neonatal concentrations at 2 and 24 hours. The corresponding neonate/mother concentration ratios varied considerably, and were not so strongly correlated to the duration of antenatal drug transfer. The results suggest that with a slowly eliminated agent like diazepam, the drug concentration in capillary blood obtained from the newborn a few hours after delivery gives a reasonably good indication of the fetal drug exposure. The transplacental passage of diazepam is rapid, with distribution equilibrium between mother and fetus approached within 5 to 10 minutes after intravenous injection of the drug.

Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women

“…Diazepam readily crosses the blood–brain barrier and the placenta by passive diffusion. It is also excreted into breast milk and recent studies show that diazepam reaches equilibrium in the feto-maternal systemic circulation 10-15 minutes after intravenous administration [6]. …”