Increased metabolism of acetaminophen in chronically alcoholic patients.
The aim of this work was to determine whether the metabolism of acetaminophen increases in chronic alcoholics, and consequently whether the production of its hepatotoxic metabolite is enhanced. For this purpose, the pharmacokinetics of acetaminophen were compared in 12 alcoholic men and 12 healthy controls. After a 12-hr fast, the patients (on the 3rd hospital day) and volunteers were given 1 g of oral acetaminophen at 8.00 AM. Venous blood samples were drawn before drug intake and at regular intervals after to evaluate plasma acetaminophen concentrations. The elimination half-life of acetaminophen was significantly shorter in the alcoholic patients than in the controls (1.70 +/- 0.55 vs. 2.84 +/- 0.30 hr, p < 0.001). Similarly, total plasma acetaminophen clearance was significantly higher in the patients than in the controls (29.19 +/- 13.37 vs. 24.45 +/- 11.10 l/hr, p < 0.05). These results confirm that the metabolism of acetaminophen increases in chronic alcoholism and consequently suggest that its potential liver toxicity might be enhanced.
Girre
C
C
Clinique Toxicologique Hospital F. Widal, Paris, France.
Hispard
E
E
Palombo
S
S
N'Guyen
C
C
Dally
S
S
D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D000437:Alcoholism / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D012307:Risk Factors
D000082:Acetaminophen