Maternofetal transfer of two benzodiazepines. Effect of plasma protein binding and placental uptake.

The influence of plasma protein binding on the maternofetal transfer of diazepam was studied in the perfused human placental lobule. Substitution of buffered salt perfusate in both maternal and fetal circuits for a perfusate with plasma proteins did not alter diazepam transfer significantly. Diazepam placental uptake was shown to be important in perfusion, with both types of perfusates. Comparison with the less liposoluble and less protein-bound benzodiazepine, fosazepam, revealed a marked difference in placental uptake but not in maternofetal transfer. In incubation studies, the kinetics of placental uptake confirmed this difference.