BACKGROUND: Multiple factors can influence blood alcohol levels (BALs) after oral ethanol intake. To minimize the variability in BALs, an alcohol "clamping" method in which alcohol is administered intravenously has been previously reported. We have modified this method and developed a multistage alcohol clamp procedure in humans. METHODS: Infusion of alcohol to achieve sequentially increasing steady-state BALs at 50, 100, and 150 mg/dl (e.g., an alcohol clamp procedure) was performed in five subjects. The method used intravenous infusion of 6% alcohol in saline and followed a protocol generated by a physiologically based pharmacokinetic model for alcohol infusion. Real-time measurement of BALs was used to base decisions for necessary adjustments in the infusion rates on a negative feedback principle to achieve and maintain the desired BALs. Additionally, in three of these subjects, breath alcohol levels were determined simultaneously with BAL measurements. RESULTS: A three-stage alcohol clamp procedure was used to achieve BALs of 50, 100, and 150 mg/dl. The intra-assay and interassay variations for measurement of BALs were 1.6 and 2.1%, respectively. The coefficients of variation for the 50, 100, and 150 mg/dl alcohol clamps were 9.8, 5.6, and 4.6%, respectively. The deviation from target BALs for the three clamps were less than 5%. Breath alcohol levels were lower than BALs across all time points, with the mean ratio between the two being 0.84. Correlation analysis showed a very strong correlation between the two alcohol measurement methods ( r= 0.96; p < 0.001). CONCLUSIONS: A three-stage alcohol clamp procedure (50, 100, and 150 mg/dl) has been developed by following a protocol generated with a physiologically based pharmacokinetic model for alcohol infusion in human subjects. This is a suitable procedure to examine the responses on cognitive measures and physiologic parameters under steady states of desired BALs.
BACKGROUND: Multiple factors can influence blood alcohol levels (BALs) after oral ethanol intake. To minimize the variability in BALs, an alcohol "clamping" method in which alcohol is administered intravenously has been previously reported. We have modified this method and developed a multistage alcohol clamp procedure in humans. METHODS: Infusion of alcohol to achieve sequentially increasing steady-state BALs at 50, 100, and 150 mg/dl (e.g., an alcohol clamp procedure) was performed in five subjects. The method used intravenous infusion of 6% alcohol in saline and followed a protocol generated by a physiologically based pharmacokinetic model for alcohol infusion. Real-time measurement of BALs was used to base decisions for necessary adjustments in the infusion rates on a negative feedback principle to achieve and maintain the desired BALs. Additionally, in three of these subjects, breath alcohol levels were determined simultaneously with BAL measurements. RESULTS: A three-stage alcohol clamp procedure was used to achieve BALs of 50, 100, and 150 mg/dl. The intra-assay and interassay variations for measurement of BALs were 1.6 and 2.1%, respectively. The coefficients of variation for the 50, 100, and 150 mg/dl alcohol clamps were 9.8, 5.6, and 4.6%, respectively. The deviation from target BALs for the three clamps were less than 5%. Breath alcohol levels were lower than BALs across all time points, with the mean ratio between the two being 0.84. Correlation analysis showed a very strong correlation between the two alcohol measurement methods ( r= 0.96; p < 0.001). CONCLUSIONS: A three-stage alcohol clamp procedure (50, 100, and 150 mg/dl) has been developed by following a protocol generated with a physiologically based pharmacokinetic model for alcohol infusion in human subjects. This is a suitable procedure to examine the responses on cognitive measures and physiologic parameters under steady states of desired BALs.
Authors: Elizabeth Ralevski; Edward B Perry; D Cyril D'Souza; Vanessa Bufis; Jacqueline Elander; Diana Limoncelli; Michael Vendetti; Erica Dean; Thomas B Cooper; Sherry McKee; Ismene Petrakis Journal: Nicotine Tob Res Date: 2011-12-16 Impact factor: 4.244
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Authors: Robert F Leeman; Elizabeth Ralevski; Diana Limoncelli; Brian Pittman; Stephanie S O'Malley; Ismene L Petrakis Journal: Psychopharmacology (Berl) Date: 2014-02-20 Impact factor: 4.530
Authors: Karin Kerfoot; Brian Pittman; Elizabeth Ralevski; Diana Limoncelli; Julia Koretski; Jenelle Newcomb; Albert J Arias; Ismene L Petrakis Journal: Alcohol Clin Exp Res Date: 2013-07-29 Impact factor: 3.455
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Authors: Caroline A Arout; Albert C Perrino; Elizabeth Ralevski; Gregory Acampora; Julia Koretski; Diana Limoncelli; Jenelle Newcomb; Ismene L Petrakis Journal: Alcohol Clin Exp Res Date: 2016-05-24 Impact factor: 3.455
Authors: Melissa A Cyders; Martin H Plawecki; William Corbin; Andrea King; Denis M McCarthy; Vijay A Ramchandani; Jessica Weafer; Sean J O'Connor Journal: Alcohol Clin Exp Res Date: 2020-03-15 Impact factor: 3.455