Intranasal administration of midazolam: pharmacokinetic and pharmacodynamic properties and sedative potential.

This study investigated the pharmacodynamic effects and sedative potential of midazolam administered by the intranasal route to adult volunteers. A double-blind, randomized, controlled study was carried out on seventeen healthy, male volunteers to study plasma level changes, sedative effects and variations in vital signs following intranasal administration of 0.2 mg/kg and 0.3 mg/kg doses of midazolam. Eight subjects received 0.2 mg/kg midazolam, seven received 0.3 mg/kg. Each subject rested for 15-20 minutes after placement of vital sign monitors and venipuncture needles before administration of midazolam. Behavior during the rest period was designated as the control so that each subject acted as his own control. Each subject's behavior was assessed on a scale of 1 (asleep) to 8 (excited). Plasma concentrations of midazolam were analyzed using venous blood samples from each of three randomly selected subjects for each of the two doses. Vital signs, monitored continuously, included electrocardiogram, heart rate, blood pressure, respiratory rate and oxygen saturation (SPO2). Plasma concentration of midazolam in both groups maintained adequate sedation levels with each group sustaining favorable sedation conditions from 15-20 minutes to 55-60 minutes. Individual variations of midazolam plasma concentration within the 0.3 mg/kg group were greater than those of the 0.2 mg/kg group. Normal vital sign variations due to the nasal instillation of midazolam were observed in both groups. Some minor respiratory depression was observed in the 0.2 mg/kg group. One instance of severe respiratory depression was observed in the higher dose group. Although both doses of midazolam were effective, no benefit was observed using a dose of 0.3 mg/kg. Indeed, a 0.3 mg/kg intranasal dose of midazolam may actually produce severe respiratory depression.

RCT Entities:   Population Interventions Outcomes