DIVERGENCE OF ETHANOL AND ACETALDEHYDE KINETICS AND OF THE DISULFIRAM-ALCOHOL REACTION BETWEEN SUBJECTS WITH AND WITHOUT ALCOHOLIC LIVER-DISEASE

Despite standardization, marked interindividual variation in the sever ity of the disulfiram-alcohol reaction (DAR) has been observed. We stu died 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 wit hout liver disease. Because acetaldehyde is thought to be the main cau se of the DAR, we studied ethanol and acetaldehyde kinetics in 13 pati ents (6 females, 7 males) with alcoholic liver disease (documented by biopsy, clinical and/or radiological findings, and by quantitative liv er function) [galactose elimination capacity (GEC) 4.2 +/- SD 1.0 mg/m in/kg; aminopyrine breath test (ABT) 0.14 +/- 0.10% dose x kg/mmol CO2 ] 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 clea rly evident in controls. Blood ethanol kinetics were similar in both g roups, C-max and area under the concentration-time curve (AUC) being 6 .27 +/- 1.82 and 368.9 +/- 72.9 mmol x min/liter in alcoholic liver di sease, 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 mu mol x min/liter in alcoholic liver disease, and 110.87 +/- 56.00 and 4162.0 +/- 2424.6 in controls. We hypothesize that the l ack of disulfiram-induced acetald hyde retention in in the alcoholic l iver disease group may be due to decreased formation of disulfiram met abolites.