title: Aminotransferase activities in healthy subjects receiving three-day dosing of 4, 6, or 8 grams per day of acetaminophen.
abstract: BACKGROUND
  This multiple-dose pharmacokinetic study has a randomized, double-blind, placebo-controlled, parallel-group design with three dosing regimens. Healthy subjects received repeated doses of acetaminophen (4 then 6 g/d or 4 then 8 g/d) or placebo.
  
  
  METHODS
  The disposition of acetaminophen and its metabolites and the tolerability of increased acetaminophen doses over 3 days of continuous consumption were characterized. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities measured throughout the study were consistent across the acetaminophen 4, 6, and 8 g/d dose levels and with placebo.
  
  
  RESULTS
  Serum aminotransferase activities did not exceed the upper limit of the reference range (ULRR), except for one subject with an AST of 43 U/L (ULRR, 42 U/L), which was not considered clinically significant. All doses were generally well tolerated.
  
  
  CONCLUSIONS
  In a multiple-dose pharmacokinetics study of 4, 6, and 8 g/d of acetaminophen for 3 days, multiple aminotransferase determinations demonstrated no clinically important elevations at 1, 1.5, or 2 times the maximum recommended acetaminophen dose.
authors.affiliation: McNeil Consumer Healthcare, Fort Washington, Pennsylvania 19034, USA. atemple@mccus.jnj.com
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Temple
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Lynch
authors.forename: Jason
authors.initials: J
authors.lastname: Vena
authors.forename: Joanna F
authors.initials: JF
authors.lastname: Auiler
authors.forename: Cathy K
authors.initials: CK
authors.lastname: Gelotte
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics*; D001219:Aspartate Aminotransferases / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase