In-vivo study of diazepam transfer across the first trimester human placenta

Diazepam transfer by the first trimester human placenta was investigated at pregnancy termination between 6 and 12 weeks of gestation. Fetal fluid samples were obtained from the exocoelomic and amniotic cavities of 65 pregnancies between 8 and 25 min following the i.v. administration of 0.1 mg/kg diazepam to the mother. Diazepam was detected in one-third of coelomic fluid samples and two-thirds of amniotic fluid samples. Maternal serum and urine diazepam concentrations correlated negatively and positively respectively, with time from drug injection to sampling. Individual diazepam concentrations were low on the fetal side, and the corresponding concentrations were independent of maternal serum concentrations and the time from drug injection to sampling. Amniotic fluid diazepam content increased significantly with advancing gestational age. A multiple regression analysis showed that the diazepam content of the coelomic fluid was not influenced by maternal serum diazepam concentration, the time from drug injection to sampling or gestational age, whereas only gestational age contributed to the diazepam content of amniotic fluid. These data demonstrate that the placental transfer of diazepam occurs from week 6 of gestation, indicate a preferential transfer of this drug to the amniotic cavity and suggest that diazepam may accumulate in fetal circulation and tissues during organogenesis.