title: Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Retrospective reports suggest that therapeutic doses of acetaminophen may be associated with fulminant hepatic failure and death in alcoholic patients. Millions of patients use acetaminophen; the prevalence of alcoholism in the United States is 5% to 10%.
  
  
  OBJECTIVE
  To determine if hepatic injury was associated with maximal therapeutic dosing of acetaminophen to chronic alcohol abuse patients immediately following cessation of alcohol intake (the presumed time of maximal vulnerability).
  
  
  METHODS
  Patients entering an alcohol detoxification center were enrolled in a randomized, double-blind, placebo-controlled trial. Exclusion criteria were baseline values of aspartate or alanine aminotransferase greater than 120 U/L, international normalized ratio greater than 1.5, serum acetaminophen level greater than 20 mg/L, or a history of ingesting more than 4 g/d of acetaminophen. Acetaminophen, 1000 mg, or placebo was administered orally 4 times daily for 2 consecutive days and liver test results were monitored for 2 more days. Acetaminophen was not administered until the alcohol had been eliminated.
  
  
  RESULTS
  There were 102 patients in the acetaminophen-treated group and 99 patients in the placebo-treated (control) group. Demographic data, alcohol history, and baseline blood test results were similar in both groups. The mean (SD) aspartate aminotransferase level on day 4 was 38.0 +/- 26.7 U/L in the acetaminophen-treated group and 37.5 +/- 27.6 U/L in the placebo-treated group. There were 4 patients in the acetaminophen-treated group and 5 in the placebo-treated group who developed an increase in their serum aspartate aminotransferase level to greater than 120 U/L; it did not exceed 200 U/L in any patient. The mean (SD) international normalized ratio on day 4 was 0.96 +/- 0.09 in the acetaminophen-treated group and 0.98 +/- 0.11 in the placebo-treated group.
  
  
  CONCLUSIONS
  Repeated administration of the maximum recommended daily doses of acetaminophen to long-term alcoholic patients was not associated with evidence of liver injury.
authors.affiliation: Rocky Mountain Poison and Drug Center, 1010 Yosemite Cir, Denver, CO 80230, USA. EKuffner@rmpdc.org
authors.forename: E K
authors.initials: EK
authors.lastname: Kuffner
authors.forename: R C
authors.initials: RC
authors.lastname: Dart
authors.forename: G M
authors.initials: GM
authors.lastname: Bogdan
authors.forename: R E
authors.initials: RE
authors.lastname: Hill
authors.forename: E
authors.initials: E
authors.lastname: Casper
authors.forename: L
authors.initials: L
authors.lastname: Darton
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology* / Q000534:rehabilitation; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D000082:Acetaminophen; D001219:Aspartate Aminotransferases