Aminotransferase activities in healthy subjects receiving three-day dosing of 4, 6, or 8 grams per day of acetaminophen.
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.
Temple
Anthony R
AR
McNeil Consumer Healthcare, Fort Washington, Pennsylvania 19034, USA. atemple@mccus.jnj.com
Lynch
Joseph M
JM
Vena
Jason
J
Auiler
Joanna F
JF
Gelotte
Cathy K
CK
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
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase