A three-stage alcohol clamp procedure in human subjects

Marappa G. Subramanian, Sarah H. Heil, Michael L. Kruger, Karen L. Collins, Philip O. Buck, Tina Zawacki, Antonia Abbey, Robert J. Sokol, Michael P. Diamond

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1479-1483
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Issue number10
StatePublished - Oct 2002
Externally publishedYes


  • Alcohol
  • Blood and Breath Alcohol Levels
  • Clamp Procedure

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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