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British Journal of Pharmacology 1986 Feb;21(2):197-204
Scavone JM, Greenblatt DJ, Harmatz JS, Shader RI.
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.
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Kinetic and dynamic interaction of brotizolam and ethanol (1986)
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03-05-2008, 13:10
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