A comparative pharmacokinetic and dynamic evaluation of alprazolam sustained-release, bromazepam, and lorazepam

Sustained-release (SR) alprazolam may facilitate compliance with oral benzo diazepine treatment of panic disorders that currently requires doses admini stered three or four times daily. To compare the pharmacokinetic, psychomot or performance, and subjective effects of alprazolam SR (1.5 mg), bromazepa m (3 mg taken three times daily), and lorazepam (1 mg taken three times dai ly), 13 male volunteers (aged 20-45 years) randomly received on four separa te occasions one of these medications or placebo. Once before and II times after drug administration, the subjects were tested using psychomotor perfo rmance tests (manual tracking and digit-symbol substitution test [DSST]) an d computerized questionnaires (such as the Tufts University Benzodiazepine Scale [TUBS], the Addiction Research Center Inventory, and the visual analo g scales) to determine the subjective effects of the drugs. Blood samples f or the determination of the plasma levels of the drugs were collected befor e and 17 times after the drug was administered. A peak plateau of plasma al prazolam began approximately 6 hours after the dose, which was later than t he initial peaks for lorazepam and bromazepam (1-2 hours after the dose). O nce this plateau had begun, alprazolam SR sustained that concentration bett er than did the other two formulations. Of the PO measures on which the res ponse averaged for the first 14 hours differed among drugs (p < 0.05), brom azepam differed from placebo on two measures, lorazepam on four (including DSST Performance and TUBS Sedation), and alprazolam SR on nine (including a ll four affected by lorazepam). Lorazepam and alprazolam, but not bromazepa m, produced significantly snore sedation than placebo. The doses of the thr ee drugs were not equipotent in sedation and mood effects. None of the drug s tested differed from placebo on measures relevant to abuse liability.