Document Detail


Hepatic ethanol elimination kinetics in patients with cirrhosis.
MedLine Citation:
PMID:  19404864     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To address the question of whether increased ethanol elimination in alcoholics can be ascribed to increased metabolism via alcohol dehydrogenase (ADH; K(m) around 0.2 mM) or the microsomal ethanol-oxidizing system (MEOS; K(m) 10 mM) by kinetic analysis of hepatic ethanol elimination in recently drinking patients with alcoholic cirrhosis and healthy subjects. A further objective was to investigate whether systemic clearance of ethanol at low arterial ethanol concentrations can be used as a measure of hepatic blood flow.
MATERIAL AND METHODS: Six patients with alcoholic cirrhosis were enrolled after 2 days of abstinence, along with 6 healthy subjects. Ethanol was administered as 6 successive infusions in increasing doses. Arterial and hepatic venous blood concentrations of ethanol were measured; hepatic blood flow was measured simultaneously. Kinetic parameters were calculated according to the sinusoidal perfusion model of enzymatic elimination by the intact liver.
RESULTS: Mean hepatic K(m) for ethanol was 0.16 mM (range 0.09-0.36) in healthy subjects and 0.36 mM (range 0.16-0.69) in patients with cirrhosis (p>0.3), both compatible with the K(m) for ADH. The two groups of subjects had similar V(max) values (p>0.3). Extrahepatic elimination of ethanol accounted for more than 50% of total elimination in both groups, which precludes the use of systemic clearance as a measure of hepatic blood flow.
CONCLUSIONS: The results support the hypothesis that ADH remains the main pathway for hepatic elimination of ethanol in recently drinking patients with alcoholic cirrhosis. We interpret this as evidence against a significant contribution of MEOS in vivo.
Authors:
Gitte Dam; Michael Sørensen; Ole Lajord Munk; Susanne Keiding
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Scandinavian journal of gastroenterology     Volume:  44     ISSN:  1502-7708     ISO Abbreviation:  Scand. J. Gastroenterol.     Publication Date:  2009  
Date Detail:
Created Date:  2009-11-20     Completed Date:  2010-02-25     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0060105     Medline TA:  Scand J Gastroenterol     Country:  England    
Other Details:
Languages:  eng     Pagination:  867-71     Citation Subset:  IM    
Affiliation:
Department of Medicine V (Hepatology), Aarhus University Hospital, Aarhus, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Alcohol Oxidoreductases / metabolism*
Case-Control Studies
Contrast Media
Cytochrome P-450 Enzyme System / metabolism*
Ethanol / pharmacokinetics*
Female
Humans
Iohexol
Liver Cirrhosis, Alcoholic / metabolism*
Male
Middle Aged
Grant Support
ID/Acronym/Agency:
1 R01 DK-074419/DK/NIDDK NIH HHS; R01 DK074419-02/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Contrast Media; 64-17-5/Ethanol; 66108-95-0/Iohexol; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.1.-/Alcohol Oxidoreductases; EC 1.1.1.-/microsomal ethanol-oxidizing system
Comments/Corrections
Comment In:
Scand J Gastroenterol. 2010 Mar;45(3):382-3; author reply 384   [PMID:  19900053 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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