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

Diazepam transfer by the first trimester human placenta wasinvestigated at pregnancy termination between 6 and 12 weeksof gestation. Fetal fluid samples were obtained from the exocoelomicand amniotic cavities of 65 pregnancies between 8 and 25 minfollowing the i.v. administration of 0.1 mg/kg diazepam to themother. Diazepam was detected in one-third of coelomic fluidsamples and two-thirds of amniotic fluid samples. Maternal serumand urine diazepam concentrations correlated negatively andpositively respectively, with time from drug injection to sampling.Individual diazepam concentrations were low on the fetal side,and the corresponding concentrations were independent of maternalserum concentrations and the time from drug injection to sampling.Amniotic fluid diazepam content increased significantly withadvancing gestational age. A multiple regression analysis showedthat the diazepam content of the coelomic fluid was not influencedby maternal serum diazepam concentration, the time from druginjection to sampling or gestational age, whereas only gestationalage contributed to the diazepam content of amniotic fluid. Thesedata demonstrate that the placental transfer of diazepam occursfrom week 6 of gestation, indicate a preferential transfer ofthis drug to the amniotic cavity and suggest that diazepam mayaccumulate in fetal circulation and tissues during organo-genesis.