Lorazepam pharmacodynamics and pharmacokinetics in children

We evaluated the effects of low doses of lorazepam on episodic versus long-term memory, attention, and somatic and affective symptoms, as well as its pharmacokinetics, in a group of 16 children aged 2.8 to 14.2 years. Psychologic assessments of each child were performed twice before intravenous administration of lorazepam (0.03 mg/kg), and 1 1/2 hours and 24 hours after lorazepam; there were no significant changes in long-term memory, attention, or somatic symptoms. There was a significant decrease in affective symptoms at 1 1/2 hours (p = 0.011), with a trend toward decreased anxiety at 1 1/2 and 24 hours after lorazepam (p = 0.026 and 0.028, respectively). There was also a selective anterograde amnestic effect in 5 of 16 children after lorazepam (p = 0.06). Mean (+/- SD) lorazepam systemic clearance was 1.3 +/- 0.4 ml/min/kg, with a terminal half-life of 10.5 +/- 2.9 hours and an unbound clearance of 15.9 +/- 5.2 ml/min/kg. A group of healthy adult volunteers who were given lorazepam had a mean systemic clearance of 1.0 +/- 0.4 ml/min/kg, somewhat less than that of the children (p = 0.069). There were no significant differences in any lorazepam pharmacokinetic parameter between those children who did versus those who did not have changes in affective symptoms or amnesia. These data should be helpful in establishing the dose of lorazepam in children, as the drug becomes more widely used as an antiemetic, premedicant, and anticonvulsant agent.