[The pharmacokinetics of midazolam following intramuscular administration]

There have been conflicting reports on the pharmacokinetics of midazolam, administered i.m. The aims of this study were to determine the pharmacokinetic data of midazolam following different doses and to test whether a correlation exists between its plasma level and sedative effect. METHODS. Fifteen patients between the ages of 18 and 50 were divided into three groups for i.m. administration of midazolam 0.05 mg/kg (group 1), 0.1 mg/kg (group 2), or 0.15 mg/kg (group 3) i.m. Venous blood was drawn 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 min, and 2, 3, 4, 6, 8 h after the injection. After the same times the sedative effect was estimated by the anesthetist (awake, sleeping but easy to wake, sleeping and difficult to wake, unconscious). The plasma midazolam levels were determined by gas chromatography. The following pharmacokinetic parameters were ascertained: Cmax (peak concentration), tmax (time to attain peak concentration), clearance, elimination half-life. RESULTS. The peak concentration is directly proportional to the dosage of midazolam and the relation between the two is linear. The median Cmax values were 35.3 ng/ml (group 1), 103 ng/ml (group 2) and 123.5 ng/ml (group 3). The duration of tmax was between 12 and 36 min (means = 27 min). There was no significant difference between the groups in clearance, tmax, or elimination half-life. A significant correlation was found between the plasma midazolam levels and the degree of sedation. However, we observed a considerable variability in the effect. CONCLUSION. A 95% confidence interval for the prediction of the peak concentration of midazolam after i.m. injection is stated. Midazolam should be administered at a dose of 0.05 mg/kg at the most, if unconsciousness after premedication is to be avoided.