Placental transfer of midazolam and its metabolite 1-hydroxymethylmidazolam in the pregnant ewe.

Plasma concentrations of midazolam and its metabolites were measured in maternal and fetal blood after intravenous administration of 90 mg of midazolam to seven pregnant ewes in whom sampling catheters had been chronically implanted. Midazolam and its metabolite 1-hydroxymethylmidazolam crossed the placenta of the pregnant ewe. The fetal/maternal plasma concentration ratio of midazolam and the metabolite was 0.15. The distribution and elimination half-lives of midazolam and the metabolite were identical in both maternal and fetal circulations. The major compound found in the urine was the metabolite 1-hydroxymethylmidazolam glucuronide.