Plasma concentrations and clinical effects after single oral doses of prazepam, clorazepate, and diazepam

In a double-blind parallel-group pharmacokinetic and pharmacodynamic study, 31 healthy volunteers received single oral doses of prazepam (10 mg), clorazepate (7.5 mg), or diazepam (5 mg). Appearance in plasma of diazepam and of desmethyldiazepam was rapid after administration of diazepam and clorazepate, respectively, with peak plasma concentrations reached within an average of 1 hour. After oral prazepam, however, desmethyldiazepam appeared in blood slowly, with the highest mean concentration at 6 hours postdosage. Clinical self-ratings of fatigue and of "feeling spacey" were significantly different among groups, with changes over baseline being more marked with clorazepate and diazepam than with prazepam. Thus, differences in absorption rate of orally administered benzodiazepines can lead to differences in the intensity of single-dose effects, despite administration of doses that are equivalent in terms of long-term anxiolytic efficacy.