title: Kinetic and dynamic interaction of brotizolam and ethanol.
abstract: Thirteen healthy male volunteers ingested a single 0.25 mg dose of the thienodiazepine hypnotic, brotizolam, on two occasions: once with a typical social cocktail (containing 60 ml of vodka), and in a second trial with an 'ethanol-placebo' cocktail. Brotizolam kinetics were determined from multiple plasma concentrations measured during the 24 h after dosage. Coadministration of brotizolam with ethanol, as opposed to the placebo cocktail, slightly imparied brotizolam clearance (1.85 vs 2.19 ml min-1 kg-1 P less than 0.005), increased peak plasma concentrations (5.3 vs 4.3 ng ml-1, P less than 0.05), and prolonged elimination half-life (5.2 vs 4.4 h, P less than 0.05). There was evidence of impairment of performance, although not statistically significant, for the first 4-6 h after brotizolam dosage in the reaction time test, the digit-symbol substitution test, and a tracking task. None of these was enhanced by ethanol. In both trials, brotizolam produced significant increases in self-rated perceptions of sedation, fatigue, feeling 'spaced-out', and thinking slowed down. These effects were more intense during the brotizolam-ethanol as compared to brotizolam-placebo. In both trials, recovery was essentially complete by 6-8 h after dosage. Coadministration of brotizolam with ethanol produces a small but significant impairment of brotizolam clearance. Brotizolam produced self-rated perceptions of sedation and fatigue during 4-6 h after dosage, but objective impairment of psychomotor performance was minimal. Subjective perceptions of sedation were enhanced by ethanol coadministration, but the effects on psychomotor performance were not.
mesh_terms: D000328:Adult; D001381:Azepines / Q000378:metabolism* / Q000494:pharmacology; D002849:Chromatography, Gas; D004347:Drug Interactions; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D013850:Thinking / Q000187:drug effects
chemical_list: D001381:Azepines; D006993:Hypnotics and Sedatives; D000431:Ethanol; C020960:brotizolam