Disulfiram treatment increases plasma and red blood cell acetaldehyde in abstinent alcoholics.
BACKGROUND
Much of alcohol's toxicity is due to its product, acetaldehyde. The role of acetaldehyde derived from endogenous sources was assessed in alcoholic patients administered disulfiram, an inhibitor of aldehyde dehydrogenase.


METHODS
The first part of the study included 23 subjects without biochemical or clinical evidence of chronic liver disease who were abstinent for 2 weeks; 11 patients were started on disulfiram (250 mg/day), whereas the other 12 were not given disulfiram and served as controls. The second part of the study included 13 alcoholic patients with clinical or pathological evidence of cirrhosis who also were administered disulfiram for 2 weeks. Plasma and red blood cell (RBC) acetaldehyde as well as serum transaminases were measured at baseline and after 1 and 2 weeks of treatment.


RESULTS
In the disulfiram-treated group of alcoholics without known cirrhosis, RBC acetaldehyde levels increased from the pretreatment value of 2.98+/-0.18 microM to 4.14+/-0.33 microM after 1 week and to 4.14+/-0.26 microM after 2 weeks of treatment (p < 0.001). Compared with the pretreatment values (2.07+/-0.24 microM), plasma acetaldehyde levels also increased after 1 week (3.18+/-0.32 microM) and 2 weeks (3.15+/-0.26 microM) of disulfiram treatment (p < 0.001). There were no significant differences in sequential levels measured in either plasma or RBC acetaldehyde levels in patients who were not administered disulfiram. In the group of cirrhotic patients, the mean baseline RBC acetaldehyde value (3.60+/-0.22 microM) was significantly higher than in noncirrhotics. Disulfiram therapy increased the RBC acetaldehyde after 1 week (4.63+/-0.27 microM, p < 0.001) and 2 weeks of treatment (4.06+/-0.28 microM, p < 0.05). Compared with baseline values, plasma acetaldehyde levels were significantly higher after 1 week but not after 2 weeks of disulfiram. There were no significant differences among serum transaminases in alcoholics administered disulfiram, although three cirrhotic patients did have clinically significant elevations.


CONCLUSIONS
In abstaining subjects given disulfiram, acetaldehyde concentrations increase, possibly due to diminished catabolism of endogenously generated acetaldehyde. Disulfiram should be given cautiously, especially in patients with cirrhosis.
Alcohol Research and Treatment Center, Bronx VA Medical Center and Mount Sinai School of Medicine, New York 10468, USA.
A S
AS
Rosman
A
A
Waraich
E
E
Baraona
C S
CS
Lieber
D000079:Acetaldehyde / Q000097:blood*; D000328:Adult; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000437:Alcoholism / Q000097:blood*; D000704:Analysis of Variance; D004221:Disulfiram / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013695:Temperance
D000427:Alcohol Deterrents; D000079:Acetaldehyde; D004221:Disulfiram