Browsing by Author "Vitvitskiy, Victor"

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    Alcohol Exposure Rate Control through Physiologically-Based Pharmacokinetic Modeling
    (Wiley, 2012) Plawecki, Martin H.; Zimmermann, Ulrich S.; Vitvitskiy, Victor; Doerschuk, Peter C.; Crabb, David; O’Connor, Sean; Psychiatry, School of Medicine
    Background: The 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. Methods: Individualized 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. Results: Intersection points for 54 of 61 subjects were within prescribed deviations (range of ± 3 mg% and ± 4 minutes from the nominal intersection point). Conclusions: Results 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.
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    Development and pilot validation of Computer-Assisted Self- Selfinfusion of Ethanol (CASE): a new method to study alcohol self- selfadministration in humans
    (Wiley, 2008-07) Zimmermann, Ulrich S.; Mick, Inge; Vitvitskiy, Victor; Plawecki, Martin H.; Mann, Karl F.; O’Connor, Sean; Psychiatry, School of Medicine
    Background: Human alcohol self-administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects' opportunity to control their brain alcohol exposure by computer-assisted i.v. self-administration. Methods: Instead of drinking, subjects could request increments of their arterial blood alcohol concentration (aBAC) of precisely 7.5 mg% at any time they wanted by pressing a button, provided their aBAC would not exceed 100 mg%. The latency between pushing the button and reaching the new aBAC peak was preset to be 2.5 minutes on the first day and was randomly changed to 1.5 or 3.5 minutes on days 2 and 3 in a crossover design. The necessary rate and amount of alcohol infusion was calculated by the software about once every second. Nine healthy social drinkers (4 females/5 males; mean age 25.0 +/- 4.0 year) participated in 3 sessions each. Outcome measures were mean and maximum observed aBAC, and the number of alcohol requests. Results: Maximum aBAC was 76.5 +/- 26.3 mg% on average over all experiments. When grouping days 2 and 3 according to latency (1.5 vs. 3.5 minutes), maximum aBAC and the number of requests in the session were significantly higher with the faster rise and all 3 outcome measures were significantly correlated between days. No such correlations were found between the first and either of the following days. Conclusions: These data suggest that CASE is practical and safe, and results in considerable alcohol exposure that can be manipulated with parameters chosen for the incremental exposure. Following 1 practice day, test-retest stability was good, suggesting a potential for use in scientific studies.
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    Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in laboratory experiments involving computer-assisted self-infusion of ethanol (CASE)
    (SpringerLink, 2009-03) Zimmermann, Ulrich S.; Mick, Inge; Laucht, Manfred; Vitvitskiy, Victor; Plawecki, Martin H.; Mann, Karl F.; O’Connor, Sean; Psychiatry, School of Medicine
    Rationale: Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls. Objectives: To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls. Materials and methods: Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party. Results: The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants. Conclusions: This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration.