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PLoS By Category | Recent PLoS Articles
Biochemistry - Gastroenterology and Hepatology - Mental Health - Neurological Disorders - Neuroscience - Public Health and Epidemiology - Radiology and Medical Imaging

Alcohol ADME in Primates Studied with Positron Emission Tomography
Published: Monday, October 01, 2012
Author: Zizhong Li et al.

by Zizhong Li, Youwen Xu, Don Warner, Nora D. Volkow

Background and Purpose

The sensitivity to the intoxicating effects of alcohol as well as its adverse medical consequences differ markedly among individuals, which reflects in part differences in alcohol's absorption, distribution, metabolism, and elimination (ADME) properties. The ADME of alcohol in the body and its relationship with alcohol's brain bioavailability, however, is not well understood.

Experimental Approach

The ADME of C-11 labeled alcohol, CH311CH2OH, 1 and C-11 and deuterium dual labeled alcohol, CH311CD2OH, 2 in baboons was compared based on the principle that C–D bond is stronger than C–H bond, thus the reaction is slower if C–D bond breaking occurs in a rate-determining metabolic step. The following ADME parameters in peripheral organs and brain were derived from time activity curve (TAC) of positron emission tomography (PET) scans: peak uptake (Cmax); peak uptake time (Tmax), half-life of peak uptake (T1/2), the area under the curve (AUC60min), and the residue uptake (C60min).

Key Results

For 1 the highest uptake occurred in the kidney whereas for 2 it occurred in the liver. A deuterium isotope effect was observed in the kidneys in both animals studied and in the liver of one animal but not the other. The highest uptake for 1 and 2 in the brain was in striatum and cerebellum but 2 had higher uptake than 1 in all brain regions most evidently in thalamus and cingulate. Alcohol's brain uptake was significantly higher when given intravenously than when given orally and also when the animal was pretreated with a pharmacological dose of alcohol.

Conclusion and Implications

The study shows that alcohol metabolism in peripheral organs had a large effect on alcohol's brain bioavailability. This study sets the stage for clinical investigation on how genetics, gender and alcohol abuse affect alcohol's ADME and its relationship to intoxication and medical consequences.