Absorption and elimination of midazolam by submucosal and intramuscular routes

Abstract

The purpose of this investigation was to compare the rate of absorption and clearance time of midazolam (Versed) when administered by the submucosal (SM) route), and the intramuscular (IM) route in ten healthy adult volunteers, ranging in age from 25 to 35 years. Each subject received midazolam 0.08 mg/kg, to a maximum of 5 mg, by the SM and IM routes at two week intervals. Vital signs and arterial oxygen saturation levels were monitored every five minutes throughout the 180 minute study period. Blood samples (3 ml) were collected via an intravenous line, prior to midazolam administration and at 2, 5, 10, 20, 30, 45, 60, 90, 120, 150 and 180 minutes, centrifuged and analyzed by gas-liquid chromatography. The mean absorption rates and the mean elimination times of the two routes were not significantly different. The mean peak absorption was reached at 10 minutes by the SM route (80.4 ng/ml) and at 20 minutes (92.0 ng/ml) by the IM route, with considerable individual variability. Vital signs were stable throughout the study period in all subjects with both routes. All subjects reported pain at the injection site during SM injection which continued for up to 48 hours. No pain related to the IM injection was reported.