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Alcohol ADME in Primates Studied with Positron Emission Tomography
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 alco...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462207/ https://www.ncbi.nlm.nih.gov/pubmed/23049712 http://dx.doi.org/10.1371/journal.pone.0046676 |
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author | Li, Zizhong Xu, Youwen Warner, Don Volkow, Nora D. |
author_facet | Li, Zizhong Xu, Youwen Warner, Don Volkow, Nora D. |
author_sort | Li, Zizhong |
collection | PubMed |
description | 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, CH(3) (11)CH(2)OH, 1 and C-11 and deuterium dual labeled alcohol, CH(3) (11)CD(2)OH, 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 (C(max)); peak uptake time (T(max)), half-life of peak uptake (T(1/2)), the area under the curve (AUC(60min)), and the residue uptake (C(60min)). 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. |
format | Online Article Text |
id | pubmed-3462207 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34622072012-10-05 Alcohol ADME in Primates Studied with Positron Emission Tomography Li, Zizhong Xu, Youwen Warner, Don Volkow, Nora D. PLoS One Research Article 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, CH(3) (11)CH(2)OH, 1 and C-11 and deuterium dual labeled alcohol, CH(3) (11)CD(2)OH, 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 (C(max)); peak uptake time (T(max)), half-life of peak uptake (T(1/2)), the area under the curve (AUC(60min)), and the residue uptake (C(60min)). 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. Public Library of Science 2012-10-01 /pmc/articles/PMC3462207/ /pubmed/23049712 http://dx.doi.org/10.1371/journal.pone.0046676 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Li, Zizhong Xu, Youwen Warner, Don Volkow, Nora D. Alcohol ADME in Primates Studied with Positron Emission Tomography |
title | Alcohol ADME in Primates Studied with Positron Emission Tomography |
title_full | Alcohol ADME in Primates Studied with Positron Emission Tomography |
title_fullStr | Alcohol ADME in Primates Studied with Positron Emission Tomography |
title_full_unstemmed | Alcohol ADME in Primates Studied with Positron Emission Tomography |
title_short | Alcohol ADME in Primates Studied with Positron Emission Tomography |
title_sort | alcohol adme in primates studied with positron emission tomography |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462207/ https://www.ncbi.nlm.nih.gov/pubmed/23049712 http://dx.doi.org/10.1371/journal.pone.0046676 |
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