Placental transfer and maternal midazolam kinetics

Abstract

Midazolam was given in a single 15-mg oral dose as a sedative the evening before elective cesarean section. Twelve hours later, levels of this new benzodiazepine were measurable in the fetomaternal entity in only 1 of 13 cases. After 15 mg midazolam orally or 0.05 mg/kg midazolam i.m. 15-60 min before elective cesarean section, there was evident transfer of drug into the placenta, but transfer took place more slowly than with diazepam. On the basis of kinetics derived from maternal serum concentrations after oral, i.m. or i.v. dosing, midazolam appears to have a rapid onset and short duration of action, which was also evident from subjective assessments by the patients. There was wide interindividual variation in the gastrointestinal absorption of midazolam in full-term pregnant women. Clinically, midazolam nevertheless seemed to be very useful for nocturnal sedation before elective cesarean section; it ensures a mean duration of sleep of about 6 h and there are virtually no detectable levels of drug in the fetomaternal entity the next morning.