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 a lcoholic patients administered disulfiram, an inhibitor of aldehyde dehydro genase. Methods: The first part of the study included 23 subjects without biochemic al or clinical evidence of chronic liver disease who were abstinent for 2 w eeks; 11 patients were started on disulfiram (250 mg/day), whereas the othe r 12 were not given disulfiram and served as controls. Toe second part of t he study included 13 alcoholic patients with clinical or pathological evide nce of cirrhosis who also were administered disulfiram for 2 weeks. Plasma and red blood cell (RBC) acetaldehyde as well as serum transaminases were m easured at baseline and after 1 and 2 weeks of treatment. Results: In the disulfiram-treated group of alcoholics without known cirrho sis, RBC acetaldehyde levels increased from the pretreatment value of 2.98 +/- 0.18 mu M to 4.14 +/-. 0.33 mu M after 1 week and to 4.14 +/-: 0.26 mu M. after 2 weeks of treatment (p < 0.001). Compared with the pretreatment v alues (2.07 +/- 0.24 mu M), plasma acetaldehyde levels also increased after 1 week (3.18 +/-: 0.32 mu M) and 2 weeks (3.15 +/- 0.26 mu M) of disulfira m treatment (p < 0.001). There were no significant differences in sequentia l levels measured in either plasma or RBC acetaldehyde levels in patients w ho were not administered disulfiram. In the group of cirrhotic patients, th e mean baseline RBC acetaldehyde value (3.60 +/- 0.22 mu M) was significant ly higher than in noncirrhotics. Disulfiram therapy increased the RBC aceta ldehyde after 1 week (4.63 +/-: 0.27 mu M, p < 0.001) and 2 weeks of treatm ent (4.06 +/- 0.28 mu M,p < 0.05). Compared with baseline values, plasma ac etaldehyde levels were significantly higher after 1 week but not after 2 we eks of disulfiram. There were no significant differences among serum transa minases in alcoholics administered disulfiram, although three cirrhotic pat ients did have clinically significant elevations. Conclusions: In abstaining subjects given disulfiram, acetaldehyde concentr ations increase, possibly due to diminished catabolism of endogenously gene rated acetaldehyde. Disulfiram should be given cautiously, especially in pa tients with cirrhosis.