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 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 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 clearly evident in controls. Blood ethanol kinetics were similar in both groups, Cmax 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 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 Cmax and AUC of acetaldehyde, respective values being 33.46 +/- 21.52 and 1463.8 +/- 762.5 mumol x min/liter in alcoholic liver disease, and 110.87 +/- 56.00 and 4162.0 +/- 2424.6 in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Wicht
F
F
Department of Clinical Pharmacology, University of Berne, Switzerland.
Fisch
H U
HU
Nelles
J
J
Raisin
J
J
Allemann
P
P
Preisig
R
R
D000079:Acetaldehyde / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D004221:Disulfiram / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000097:blood* / Q000534:rehabilitation; D008297:Male; D008875:Middle Aged
D000431:Ethanol; D000079:Acetaldehyde; D004221:Disulfiram