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Alcoholism Clinical and Experimental Research
Article . 2012 . Peer-reviewed
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Alcohol Exposure Rate Control Through Physiologically Based Pharmacokinetic Modeling

Authors: Sean O'Connor; Martin H. Plawecki; Victor Vitvitskiy; Peter C. Doerschuk; David W. Crabb; Ulrich S. Zimmermann;

Alcohol Exposure Rate Control Through Physiologically Based Pharmacokinetic Modeling

Abstract

BackgroundThe instantaneous rate of change of alcohol exposure (slope) may contribute to changes in measures of brain function following administration of alcohol that are usually attributed to breath alcohol concentration (BrAC) acting alone. To test this proposition, a 2‐session experiment was designed in which carefully prescribed, constant‐slope trajectories of BrAC intersected at the same exposure level and time since the exposure began. This paper presents the methods and limitations of the experimental design.MethodsIndividualized intravenous infusion rate profiles of 6% ethanol (EtOH) that achieved the constant‐slope trajectories for an individual were precomputed using a physiologically based pharmacokinetic model. Adjusting the parameters of the model allowed each infusion profile to account for the subject's EtOH distribution and elimination kinetics. Sessions were conducted in randomized order and made no use of feedback of BrAC measurements obtained during the session to modify the precalculated infusion profiles. In one session, an individual's time course of exposure, BrAC(t), was prescribed to rise at a constant rate of 6.0 mg% per minute until it reached 68 mg% and then descend at −1.0 mg% per minute; in the other, to rise at a rate of 3.0 mg% per minute. The 2 exposure trajectories were designed to intersect at a BrAC (t = 20 minutes) = 60 mg% at an experimental time of 20 minutes.ResultsIntersection points for 54 of 61 subjects were within prescribed deviations (range of ±3 mg% and ±4 minutes from the nominal intersection point).ConclusionsResults confirmed the feasibility of applying the novel methods for achieving the intended time courses of the BrAC, with technical problems limiting success to 90% of the individuals tested.

Keywords

Adult, Male, Time Factors, Ethanol, Brain, Central Nervous System Depressants, Models, Theoretical, Breath Tests, Humans, Female, Infusions, Intravenous

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    15
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    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
15
Top 10%
Average
Average
bronze