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Divergence of Ethanol and Acetaldehyde Kinetics and of the Disulfiram‐Alcohol Reaction between Subjects with and without Alcoholic Liver Disease
Author(s) -
Wicht Francis,
Fisch HansUlrich,
Nelles Joachim,
Raisin Juergen,
Allemann Peter,
Preisig Rudolf
Publication year - 1995
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1995.tb01515.x
Subject(s) - acetaldehyde , alcoholic liver disease , liver disease , medicine , cmax , ethanol , gastroenterology , nausea , liver function tests , disulfiram , alcohol , endocrinology , chemistry , pharmacology , pharmacokinetics , cirrhosis , biochemistry
Despite standardization, marked interindividual variation in the severity of the disulfiram‐alcohol reaction (DAR) has been observed. We studied the DAR in 51 consecutive alcoholics with ( n = 16) and without ( n = 35) significant alcoholic liver disease. Clinical signs of the DAR were much weaker in the patients with compared with those patients without liver disease. Because acetaldehyde is thought to be the main cause of the DAR, we studied ethanol and acetaldehyde kinetics in 13 patients (6 females, 7 males) with alcoholic liver disease (documented by biopsy, clinical and/or radiological findings, and by quantitative liver function) [galactose elimination capacity (GEC) 4.2 ± SD 1.0 mg/min/kg; aminopyrine breath test (ABT) 0.14 ± 0.10% dose × kg/mmol CO 2 ] and 13 age‐ and sex‐matched controls (alcoholics without significant liver disease, GEC 7.1 ± 0.7; ABT 0.81 ± 0.35). Clinical signs of acetaldehyde toxicity during the DAR (flush, nausea, tachycardia, and blood pressure drop) were absent in alcoholic liver disease, but clearly evident in controls. Blood ethanol kinetics were similar in both groups, C max and area under the concentration‐time curve (AUC) being 6.27 ± 1.82 and 368.9 ± 72.9 mmol × min/liter in alcoholic liver disease, and 6.62 ± 1.71 and 377.6 ± 124.5 in controls, respectively. In contrast, there was a strong ( p < 0.001) difference in C max and AUC of acetaldehyde, respective values being 33.46 ± 21.52 and 1463.8 ± 762.5 μmol × min/liter in alcoholic liver disease, and 110.87 ± 56.00 and 4162.0 ± 2424.6 in controls. We hypothesize that the lack of disulfiram‐induced acetaldehyde retention in the alcoholic liver disease group may be due to decreased formation of disulfiram metabolites.