Midazolam and diazepam: maternal and fetal effects in the pregnant ewe

Maternal and fetal hemodynamic effects and placental transfer of midazolam (RO 21-3981, Hoffman-LaRoche) and diazepam were studied in chronically instrumented pregnant ewes. Diazepam administration resulted in greater increases of maternal and fetal heart rates and maternal blood pressure, and greater alteration of total uterine blood flow than did administration of comparable doses of midazolam. Neither drug altered fetal mean arterial pressure or maternal and fetal respiratory gases. Although the absolute blood concentrations were higher, the fetal:maternal drug concentration ratios were consistently less for midazolam than for diazepam, suggesting less placental permeability of midazolam.