Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo

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Abstract
Thirty-nine healthy volunteers received single oral doses of either alprazolam (1 mg), lorazepam (2 mg), prazepam (20 mg), or placebo in a randomized, double-blind, parallel group study. Plasma drug concentrations, subjective self-ratings, and the digit symbol substitution test (DSST) were evaluated during 24 hours after dosage. Alprazolam was absorbed rapidly and produced correspondingly rapid sedation and impaired DSST performance. These effects also resolved rapidly, being similar to placebo by 4 to 6 hours after dosage. Sedative and DSST-impairing effects of lorazepam were of slower onset but longer duration than those of alprazolam. After oral prazepam, appearance of desmethyldiazepam in plasma was slow, with minimal sedative and DSST-impairing effects. Twenty-four hours after dosage, both alprazolam and lorazepam significantly impaired recall of a list of 16 words learned previously 3 hours after dosage. Thus benzodiazepines with approximately equivalent clinical anxiolytic properties may have different sedative, performance-impairing, and amnesic profiles after single doses in healthy volunteers; these differences are explained at least in part by pharmacokinetic variations.