Pharmacokinetics of Alcohol Following Single Low Doses to Fasted and Nonfasted Subjects

Welling, Peter G.; Lyons, Lyman; Elliott, Richard L.; Amidon, Gordon L.

doi:10.1177/009127007701700403

Cited by 54 publications

(24 citation statements)

References 12 publications

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“…Small variations in the composition of the meal can have very significant effects on alcohol absorption [30]. Great inter-and intra-subject variability in gastric emptying has been demonstrated even with a strictly standardized protocol of meals [19,29,31].…”

Section: Discussionmentioning

confidence: 99%

Inter‐individual and intra‐individual variability of ethanol concentration‐time profiles: comparison of ethanol ingestion before or after an evening meal.

Fraser

Rosalki

Gamble

et al. 1995

Brit J Clinical Pharma

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1. The magnitude of the variability of ethanol absorption is an important factor for studies that seek to determine the significance of potential interactions between ethanol and drugs. The aim of this study was to determine the extent of inter‐ and intra‐individual variability of ethanol concentration‐time profiles in fasted and fed subjects. 2. Twenty‐four healthy male subjects were randomized to receive ethanol 0.3 g kg‐1 before an evening meal on two study days and ethanol 0.3 g kg‐1 after an evening meal on two study days. Plasma ethanol concentrations were measured at intervals from 0‐240 min. 3. There were significant differences in the mean area under the ethanol concentration‐time curve (AUC), the mean peak ethanol concentration (Cmax), the mean ethanol elimination slope and the time to peak ethanol concentration between the fed and fasted subjects. There were no significant differences between the first and second study days for either fed or fasting subjects for all parameters. 4. There was no statistically significant difference in inter‐ or intra‐subject variance between fed and fasted studies although the coefficients of variation (standard deviation expressed as a percentage of the mean) for the differences between the first and second study day were higher for fed studies. 5. The large inter‐ and intra‐individual variability of alcohol absorption for both fasted and fed subjects must be considered in the design of alcohol‐drug interaction studies.

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Section: Discussionmentioning

confidence: 99%

Inter‐individual and intra‐individual variability of ethanol concentration‐time profiles: comparison of ethanol ingestion before or after an evening meal.

Fraser

Rosalki

Gamble

et al. 1995

Brit J Clinical Pharma

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“…The rate of absorption is also influenced by other factors, such as the rate of gastric emptying, ingested food and the enterohepatic circulation of ethanol (13,14). However, consistent with previous reports (15 , 16) the plasma ethanol concentrations did not necessarily reflect the intraluminal concentrations and the peak plasma level usually occurred at a time when the intraluminal level had already started to decline .…”

Section: Discussionmentioning

confidence: 99%

The in vivo effect of ethanol on gastrointestinal motility and gastrointestinal handling of calcium in rats.

Krishnamra

Limlomwongse

1987

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryThe acute effects of an intragastric administration of ethanol (2g/kg body weight) (given as 13.3% w/v solution) on the in vivo gastrointestinal motility and gastrointestinal absorption and secretion of calcium were investigated in 20-h fasted rats. Gastric ethanol con centration remained high for 90min while the concentration in the duodenum peaked at 30min before declining to a range slightly higher than that in the mid and distal intestine. Plasma ethanol peaked at 60min. From the polyethylene glycol (PEG) distribution, ethanol was found to delay gastric emptying, and at 60min, 40% of PEG was still retained in the stomach of the ethanol-treated group while gastric emptying had been completed in the controls. However, ethanol placed directly into the duodenum was found to enhance intestinal motility.Under control conditions, exogenous calcium was completely ab sorbed by the time it reached the mid-small intestine (J3) and calcium found in more distal segments was of endogenous origin. Ethanol sup pressed calcium absorption while markedly stimulating calcium secretion in the stomach and the distal small intestine, resulting in a net 32% in crease in the total gastrointestinal calcium content. This effect on the distal small intestine was from ethanol that had reached this area from the circulation, and not from ethanol transit along the gastrointestinal tract.

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“…Timing of B1 and PAS LTP after tablet and drink intake (cf. Figure 1) was planned according to the expected times of peak plasma concentration of APZ, ZLP, and EtOH in healthy young adults (de Haas et al, 2010;Greenblatt and Wright, 1993;Welling et al, 1977).…”

Section: Experimental Designmentioning

confidence: 99%

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

Lücke

Heidegger

Röhner

et al. 2014

Neuropsychopharmacol

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Ingesting ethanol (EtOH) at low doses during social drinking is a common human behavior for its facilitating effects on social interactions. However, low-dose EtOH may have also detrimental effects that so far are underexplored. Here we sought to test the effects of lowdose EtOH on long-term potentiation (LTP)-like plasticity in human motor cortex. Previous cellular experiments showed that low-dose EtOH potentiates extrasynaptic GABAAR and reduces NMDAR-mediated currents, processes that would limit the expression of LTP. Paired associative transcranial magnetic stimulation (PAS LTP ) was employed in nine healthy subjects for induction of LTP-like plasticity, indexed by a long-term increase in motor-evoked potential input-output curves. Synaptic a1-GABAAR function was measured by saccadic peak velocity (SPV). Very low doses of EtOH (resulting in blood concentrations of o5 mM) suppressed LTP-like plasticity but did not affect SPV when compared with a placebo condition. In contrast, 1 mg of alprazolam, a classical benzodiazepine, or 10 mg of zolpidem, a non-benzodiazepine hypnotic, decreased SPV but did not significantly affect LTP-like plasticity when compared with placebo. This double dissociation of low-dose EtOH vs alprazolam/zolpidem effects is best explained by the putatively high affinity of EtOH but not alprazolam/zolpidem to extrasynaptic GABAARs and to NMDARs. Findings suggest that enhancement of extrasynaptic GABAARmediated tonic inhibition and/or reduction of NMDAR-mediated neurotransmission by EtOH blocks LTP-like plasticity in human cortex at very low doses that are easily reached during social drinking. Therefore, low-dose EtOH may jeopardize LTP-dependent processes, such as learning and memory formation.

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Pharmacokinetics of Alcohol Following Single Low Doses to Fasted and Nonfasted Subjects

Cited by 54 publications

References 12 publications

Inter‐individual and intra‐individual variability of ethanol concentration‐time profiles: comparison of ethanol ingestion before or after an evening meal.

Inter‐individual and intra‐individual variability of ethanol concentration‐time profiles: comparison of ethanol ingestion before or after an evening meal.

The in vivo effect of ethanol on gastrointestinal motility and gastrointestinal handling of calcium in rats.

Deleterious Effects of a Low Amount of Ethanol on LTP-Like Plasticity in Human Cortex

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